Category: 13444-24-1

Naruto, Shunsuke published the artcileSynthesis and spasmolytic activity of aminoalkyl 2-substituted 2-(1,2-benzisoxazol-3-yl)acetates, Recommanded Product: 1-Ethylpiperidin-3-ol, the publication is Chemical & Pharmaceutical Bulletin (1987), 35(5), 2095-100, database is CAplus and MEDLINE.

Several aminoalkyl esters (I, II, and III, R = aminoalkyl or alkylpiperidino of 2-(1,2-benzisoxazol-3-yl)-2-cyclohexylacetic acid, 1-(1,2-benzisoxazol-3-yl)-1-cyclopentanecarboxylic acid, and 1-(1,3-benzisoxazol-3-yl)-1-cyclohexanecarboxylic acid and their quaternary ammonium salts were prepared Me 1,2-benzisoxazole-3-acetate was treated with NaH and then cyclohexyl iodide or Br(CH₂)₄Br or Br(CH₂)₅Br to give esters which were hydrolyzed and esterified to give I–III, resp. The anticholinergic (anti-Ach) and musculotropic (anti-KCl) activities of these compounds were examined 3-(N,N-Diethylamino)propyl 2-(1,2-benziosoxazol-3-yl)-2-cyclohexylacetate [I, R = (CH₂)₃NEt₂] showed potent anti-Ach and anti-KCl activities.

Chemical & Pharmaceutical Bulletin published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C7H15NO, Recommanded Product: 1-Ethylpiperidin-3-ol.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Paul, Raymond published the artcileA new synthesis of N-substituted 3-hydroxypiperidines, Formula: C7H15NO, the publication is Compt. rend. (1945), 560-2, database is CAplus.

When a mono-alkyl- or aryltetrahydrofurfurylamine (I) is treated with 2 mols. of HBr, the ring is apparently opened and the intermediate haloamino alc. is converted to the corresponding alkyl- or aryl-3-hydroxypiperidine (II) by the action of heat and alkali. Various I were made in 2 ways: (1) by heating tetrahydrofurfuryl chloride with a large excess of primary amine at 100° for 10 h.; (2) by hydrogenation at 100°, with Raney Ni, of 1 mol. of furfural and 1 mol. of primary amine in alc. The data for the I are given below in the order b.p., d₄, n_D, and m.p. of picrate: alkyl = Me 155-6° (b₉ 40°), 0.928/21.5°, 1.4436/21.5°, 129°; Et 170-1° (b₁₂ 62°), 0.913/21°, 1.4430/21°, 98°; Pr b₁₀ 69°; Ph b₉ 154°, 1.071/21°, 1.5617/21°, 117°; benzyl b₁₁ 151°, 1.024/21°, 1.5240/21°, 135°; 3-pyridyl, b₆ 160-1°, 1.172/23°, 1.5950/23°, 161°. One mol. I is treated with 2 mols. dry HBr and warmed at 100° for 3 h. A little water is added and the solution neutralized carefully with NH₃. The Me and Et derivatives of II are salted out with K₂CO₃, the others sep. first as oils, which on treatment with concentrated KOH give II. They are colorless, very soluble in water, strongly alk. Data for derivatives of II are given in the order b.p., d₄, n_D, m.p. of HCl salt of benzoate ester; alkyl = Me b₁₆ 79°, 0.9635/16°, 1.4695/16°, 194°; Et b₁₆ 93°, 0.9580/14°, 1.4769/14°, 204°; Pr b₁₅ 77°, 0.971/15°, 1.4589/15°, 176°; Ph b₂ 145-146°, 1.092/21°, 1.5756/21°, oily, 141° (m.p. picrate); benzyl b₁₂ 155-156, 1.056/16°, 1.5402/16°, oily. The Et and Ph derivatives are identical with those found earlier. Unsubstituted I could not be converted into unsubstituted II.

Compt. rend. published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C7H15NO, Formula: C7H15NO.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Biel, John H. published the artcileAntispasmodics. II. Derivatives of N-substituted-3-piperidols, Recommanded Product: 1-Ethylpiperidin-3-ol, the publication is Journal of the American Chemical Society (1955), 2250-6, database is CAplus.

cf. C.A. 48, 694a. The initial finding (loc. cit.) that the replacement of Et₂NCH₂CH₂ by N-ethyl-3-piperidyl in some standard antispasmodic agents yielded compounds of superior spasmolytic activity prompted a more general investigation of the therapeutic usefulness of a variety of 3-piperidyl derivatives Five classes of compounds were synthesized: (1) substituted acetic acid esters of 3-hydroxypiperidine and 3-mercaptopiperidine derivatives; (2) substituted carbamates of N-methyl-3-hydroxypiperidine; (3) N-substituted-3-piperidyl benzhydryl ethers, as well as their thio isosteres; (4) p-aminobenzoates of N-alkyl-3-piperidol; (5) N-methyl-3-piperidyldiphenylmethyl derivatives RCPh₂Y with Y = CONH₂ and CN. The 1st series of compounds yielded a number of potent antispasmodic agents, of which the disubstituted hydroxyacetates appeared to be the most promising ones. The carbamates in series 2 either inhibited or potentiated acetylcholine spasms in the guinea pig ileum depending on the type of substituent. The benzhydryl ethers (series 3) were active spasmolytic agents. Quaternization of the N produced a 10-fold increase in spasmolytic activity. The compounds in series 4 were local anesthetics comparable to procaine in potency. The diphenylacetamide derivatives (5) were moderate antispasmodics. Phenyl-2-thienylglycolic acid was obtained via a mixed benzoin condensation followed by a benzilic acid type rearrangement. The preparation of 3-mercaptopiperidines is described. A general method for obtaining N-aryl-substituted carbamates was developed. BzH (21.2 g.) and 22.4 g. 2-thiophenecarboxaldehyde in 100 cc. absolute EtOH treated with 20 g. KCN in 40 cc. H₂O, the mixture refluxed 1.5 h. with stirring, treated with 250 cc. 50% aqueous EtOH and refrigerated, the orange-yellow precipitate filtered, washed with H₂O, stirred with 10% aqueous NaHCO₃, filtered, suspended in dilute aqueous K₂CO₃, filtered, washed with H₂O, and recrystallized from aqueous EtOH yielded 21.5 g. 2-thienyl α-phenyl-α-hydroxymethyl ketone (I), m. 132-4°. I (10.6 g.), 5.0 g. NH₄NO₃, 0.1 g. Cu(OAc)₂, and 35 cc. 80% aqueous AcOH refluxed 1.5 h. with stirring, cooled, seeded, allowed to crystallize, diluted with H₂O, and filtered, and the filter cake washed with H₂O gave 10.1 g. Ph 2-thienyl diketone (II), m. 59-60°. II (15.0 g.) in 30 cc. 95% EtOH added to 15 g. KOH in 30 cc. H₂O, the mixture refluxed 10 min., the EtOH distilled off, the residual aqueous alk. solution acidified with dilute HCl, and the precipitate washed with H₂O, recrystallized from 100 cc. C₆H₆, and decolorized with 5 g. Darco yielded 7.3 g. phenyl-2-thienylglycolic acid, white crystals, m. 127-9°. N-Methyl-3-hydroxypiperidine (230 g.) and 484 g. Me benzilate in 3.0 l. heptane refluxed with stirring to solution, the refluxing solution treated with 10.0 g. NaOMe in 2.0-g. portions during 8-9 h. while removing 75 cc. MeOH, the mixture concentrated to 0.5 volume and diluted with 2 l. Et₂O, the Et₂O-heptane solution washed, dried, and filtered, the solvent removed in vacuo, the oily residue dissolved in 1300 cc. iso-PrOH, the solution acidified with HCl in Et₂O, and the precipitate filtered gave 555 g. N-methyl-3-piperidyl benzilate HCl salt, m. 221-3°; activity against acetylcholine-induced spasms in the guinea pig ileum 0.6 (atropine 1.0) (the spasmolytic activities will be given in parentheses); free base, b_0.20 198-9°; methobromide, m. 234-6° (0.50). Similarly were prepared the following esters of 1-methyl-3-piperidol (acid, b.p./mm. of base, m.p. of HCl salt, m.p. of methobromide given): Ph₂CHCO₂H, -, – (0.01), -; Ph₂NCO₂H, 190-2°/0.15, 215-16° (0.001), 273-4° (0.001); phenylthienylglycolic acid, -, 227-8° (2.0), -; HOCH₂CHPhCO₂H, 160-8°/0.10, -, [H₂SO₄ salt, m. 75° (decomposition) (0.10)], -. 1-Butyl-3-hydroxypiperidine (8.0 g.) and 6.0 g. Et₃N in 50 cc. C₆H₆ treated with stirring with 11.5 g. Ph₂CHCOCl in 50 cc. C₆H₆ below 70°, the mixture held 2 h. at 70° and filtered, and the filtrate fractionated in vacuo yielded 15.5 g. 1-butyl-3-piperidyl diphenylacetate (III), b_0.10 188-91°; III treated in iso-PrOH with MeBr gave III.MeBr, m. 143-5° (0.006). Similarly was prepared the benzilate analog HCl salt (0.06) and the methobromide, m. 144-6° (0.20). Phenylcyclohexylglycolic acid (31.0 g.), 25.0 g. 1-ethyl-3-chloropiperidine, 70 cc. absolute iso-PrOH refluxed 20 h., the solvent distilled off, the residual oil neutralized with dilute aqueous HCl and extracted with Et₂O, the aqueous phase basified with NaOH and extracted with Et₂O, and the extract dried, and distilled gave 24.0 g. 1-ethyl-3-piperidyl phenylcyclohexylglycolate (IV), b_0.05 166-7°; HCl salt, m. 215-17° (0.20). Similarly were prepared the following esters of 1-ethyl-3-piperidol (acid, b.p./mm., and m.p. HCl salt given): Ph₂CHCO₂H, -, – (0.01) [methobromide (0.07)]; Ph₂CHCSOH, -, – (0.20); phenylcyclohexylacetic acid, -, – (0.06); phenylcyclopentylacetic acid, 154-78°/0.04, 181-3° (0.05); phenylcyclopentylglycolic acid, 201°/0.40, 205-7° (0.75); phenylpropylglycolic acid, 150°/10, 166-7° (0.10); phenylthienylglycolic acid, -, 181-2° (0.30); dicyclohexylacetic acid, 151-61°/0.10, 184-5° (0.01); cyclopentylpropylacetic acid, 118-20°/0.03, 116-18° (0.01). In the same general manner were prepared the following esters: 1-isopropyl-3-piperidyl diphenylacetate, b_0.55 180-4°; HCl salt, m. 134-6° (0.002); 1-(β-phenylisopropyl)-3-piperidyl diphenylacetate HCl salt, m. 161-2° (0.0014); 1-methyl-3-piperidyl acetate methiodide, m. 171-2°. 1-Methyl-3-hydroxypiperidine (V) (23.0 g.) in 150 cc. iso-PrOH treated slowly with stirring with 37.0 g. p-O₂NC₆H₄COCl, the mixture refluxed 3 h. with stirring, cooled, and filtered, and the crude product recrystallized from EtOH gave 32 g. 1-methyl-3-piperidyl p-nitrobenzoate HCl salt (VI), m. 218-19°. VI (15.0 g.) in EtOH hydrogenated over 3.0 g. 10% Pd-C at 60 lb. pressure, and the mixture filtered and evaporated in vacuo yielded 13.0 g. p-aminobenzoate HCl salt of 1-methyl-3-piperidol (VII), m. 126° (slow decomposition). Me₂NCOCl (32.3 g.), 34.5 g. V, and 100 cc. dry pyridine refluxed 3 h., cooled, and poured into 700 cc. ice water, the mixture treated with solid NaOH and extracted with Et₂O, and the extract dried and distilled gave 44 g. N,N-dimethylcarbamate of VII, b_3.0 101-3°; methobromide, m. 205-6° (0.00005); (HCl salt, m. 198-9°); the base treated in Me₂CO with an equivalent amount PhCH₂Cl, the solution kept 3 wk at room temperature, and the precipitate filtered gave 7.0 g. PhCH₂Cl salt, m. 199-201°. NaNH₂ (10.8 g.) in 75 cc. dry PhMe treated with 36.6 g. PhCH₂NHPh in 40 cc. dry PhMe, the mixture refluxed 3 h. with stirring, treated with 19.1 g. ClCO₂Me in 40 cc. PhMe, refluxed 4 h. with stirring, and filtered, and the filtrate fractionated gave 36.5 g. Ph(PhCH₂)NCO₂Me (VIII), b_0.035 132-3°. V (19.2 g.) in 600 cc. heptane treated with 40.2 g. VIII, the mixture refluxed and treated with 1.3 g. NaOMe, the MeOH separated through a Dean-Stark trap, the residual mixture concentrated to 0.5 volume, diluted with 300 cc. Et₂O, and filtered, the filtrate washed, dried, and evaporated, and the residual oil fractionated in vacuo yielded 19.3 g. N-phenyl-N-benzylcarbamate of V, b_0.025 169-71°; methobromide, m. 123-4° (0.006). In a similar manner was prepared dibutylcarbamate of V, b_1.0 111-12°; methiodide, m. 103-4° (0.005). In the usual manner was also prepared 1-ethyl-3-piperidyl p-aminobenzoate-HCl, m. 120° (decomposition). V (11.5 g.) added to 2.3 g. molten Na in 150 cc. hot PhMe, the solution refluxed with stirring, treated with 24.7 g. Ph₂CHCl, refluxed 5 h. with stirring, and filtered, the filtrate extracted with 10% HCl, the acid extract washed with Et₂O, made strongly alk., and extracted with Et₂O, and the extract dried and distilled gave 4.5 g. benzhydryl ether (IX) of V, b_0.11 160-1°; IX.HCl, m. 70° (decomposition) (0.01); IX.MeBr, m. 186-7° (0.10) (from iso-PrOH). Ph₂CHCl (40.4 g.) and 46.0 g. V in 100 cc. PhMe refluxed 24 h. with stirring, the mixture filtered, and the filtrate fractionated gave 37.0 g. IX, b_0.08 140-7°. NaOH (13.5 g.) in 27 cc. H₂O added with stirring to 25.1 g. [Ph₂CHSC(NH₂)₂] Cl and 90 cc. EtOH, the mixture stirred 0.5 h. at 40°, treated with 15.4 g. 1-ethyl-3-chloropiperidine (X), refluxed 2 h. with stirring, cooled, poured into 500 cc. H₂O, and extracted with Et₂O, and the extract dried and distilled gave 23.1 g. 1-ethyl-3-piperidyl thiobenzhydryl ether (XI), oil, which was too heat-labile to be distilled XI in Et₂O-iso-PrOH treated with HCl in Et₂O gave XI.HCl, m. 145-6°; XI.MeBr, m. 158-61° (0.075). X (133 g.) and 69 g. AcSH in 500 cc. absolute iso-PrOH refluxed 15 h., the alc. distilled off, the oily residue treated with 250 cc. H₂O and 400 cc. Et₂O, the mixture treated with 134 g. K₂CO₃ in 200 cc. H₂O, the aqueous phase extracted repeatedly with Et₂O, and the extract dried and distilled gave 87.4 g. 1-ethyl-3-piperidyl thioacetate (XII), b_0.35 66°, n_D²⁰ 1.4963. XII (88.3 g.) added with stirring at room temperature to 1200 cc. 6% aqueous NaOH, the mixture stirred 2 h. at 20°, the solution neutralized with 94 cc. glacial AcOH, saturated with 800 g. (NH₄)₂SO₄, and extracted continuously with Et₂O, and the extract distilled gave 39 g. 1-ethyl-3-mercaptopiperidine (XIII), b_1.7 57.5°, n_D²⁰ 1.4956. XIII (11.7 g.) in 25 cc. treated with stirring and cooling with 14.8 g. p-O₂NC₆H₄COCl in 50 cc. PhMe, the solution refluxed 0.5 h., cooled, and filtered, and the filter residue recrystallized twice from iso-PrOH yielded 19.3 g. 1-ethyl-3-piperidyl p-nitrothiobenzoate-HCl salt, white crystals, m. 149-51°. Ph₂CHCN (116 g.) and 23.4 g. NaNH₂ in 500 cc. dry PhMe refluxed 6 h. with stirring, the hot mixture treated with 160 g. X in 200 cc. dry PhMe, the mixture stirred 20 h. with refluxing, cooled, and extracted with 10% aqueous HCl, the acid extract washed with Et₂O, made alk. with 200 g. KOH in 200 cc. H₂O, and extracted with Et₂O, and the extract dried and fractionated yielded 140 g. 1-methyl-x-(diphenylcyanomethyl)piperidine (XIV), b_0.05 182-6°. XIV (58.0 g.) in 250 cc. EtOH treated with 19.0 g. MeBr, the mixture kept 3 days at room temperature, the precipitate filtered off to yield 40.0 g. product (fraction A), m. 259-61° (decomposition), the filtrate evaporated to dryness, the residue suspended in 200 cc. iso-PrOH, and the insoluble material filtered off yielded 33.0 g. product (fraction B), m. 255-63° (decomposition); the filtrate evaporated to dryness gave 4.5 g. addnl. B; A recrystallized twice from EtOH yielded 30.0 g. XIV.MeBr, m. 263-5° (decomposition); B recrystallized 3 times from iso-PrOH yielded 17.0 g. isomeric XIV.MeBr, m. 278-81° (decomposition); a mixture of A and B melted at 238-42° (decomposition). XIV (50 g.) heated 3 h. on the steam bath with 500 cc. 90% H₂SO₄, the mixture poured onto ice, neutralized with 700 cc. concentrated NH₄OH, and extracted with Et₂O, the white solid separating in the aqueous and the Et₂O phase filtered off to yield 6.4 g. material (fraction C), m. 216-24°, the Et₂O distilled off, the residue suspended twice in 100 cc. boiling Me₂CO and filtered to give 10.3 g. insoluble material (fraction D), m. 227-8°, the combined Me₂CO filtrates evaporated to dryness, and the oily residue crystallized from Et₂O, and the Et₂O suspension filtered gave 5.2 g. material (fraction E), m. 150-3°. C and D combined and recrystallized from 5:1 CHCl₃-heptane yielded 6.0 g., material (fraction F), m. 228-30°. E (3.08 g.) in 25 cc. Me₂CO and 5 cc. iso-PrOH treated with 0.95 g. MeBr yielded 3.90 g. gave 1-methyl-x-diphenylcarboxamidomethylpiperidine (XV).MeBr, m. 259-60° (decomposition). F (2.5 g.) in 25 cc. EtOH gave with 0.70 g. MeBr 1.8 g. isomeric XIV.MeBr, m. 315-16°.

Journal of the American Chemical Society published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C7H15NO, Recommanded Product: 1-Ethylpiperidin-3-ol.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Shapiro, Seymour L. published the artcileAntihypertensive agents. III. Dialkylaminoalkoxypiperidines and related compounds, Computed Properties of 13444-24-1, the publication is Journal of Organic Chemistry (1960), 291-3, database is CAplus.

cf. CA 52, 18396h; 54, 6775c. Reductive alkylation of N-alkyl-3-piperidinols with HCHO and AcH, resp., gave 73% N-methyl-3-piperidinol, b₄₀ 103-4°, and 51% N-ethyl-3-piperidinol, b₄₀ 126-8°. 3-Pyridinemethanol (66.8 g.) in 500 ml. MeCN cooled to -5° during the addition of 95 g. MeBr, and the mixture stored 20 hrs. at 20° gave 89 g. 3-(hydroxymethyl)-1-methylpyridinium bromide, m. 92-4° (iso-PrOH-isopropyl ether). 1-Hydroxymethyl-3-piperidinomethanol-HBr, prepared in 70% yield, m. 113-15° (alc.-MeCOEt). 4-Pyridinemethanol (89.1 g.) and 133 g. EtBr in 800 ml. MeCN refluxed 24 hrs. gave 170 g. crude 4-hydroxymethyl-1-ethylpyridinium bromide (I). Crude I hydrogenated directly and converted into the base with 40% NaOH, and the mixture salted, extracted with Et₂O, and dried gave 31% 4-hydroxymethyl-1-ethylpiperidine. 2-Pyridinemethanol (22 g.) and 40.7 g. PhCH₂CH₂Br in 250 ml. MeCN refluxed 22 hrs. gave 19 g. 2-hydroxymethyl-1-phenethylpyridinium bromide (II), m. 158-9° (alc.). II (14 g.) in 250 ml. alc. and 1.3 g. 5% Rh on C on complete hydrogenation after 3 hrs. gave 10 g. 1-phenethyl-2-piperidinemethanol-HBr, m. 157-8°. NaH (3.1 g.) in 50 ml. PhMe treated during 40 min. with 15.4 g. 1-ethyl-3-piperidinol in 50 ml. PhMe, stirred 2 hrs. at 20°, then refluxed 2 hrs., treated over 1 hr. with 38.4 g. Me₂N(CH₂)₃Cl.HCl in H₂O, made basic, extracted with PhMe, and the mixture refluxed 6 hrs. gave 9.8 g. 3-(3-dimethylaminopropoxy)-1-ethylpiperidine (III). Addition of 3.2 g. III in 10 ml. MeCN to 4.7 g. MeI in 15 ml. MeCN after 20 hrs. gave 4.7 g. 3-(3-dimethylaminopropoxy)-1-ethyl-1-methylpiperidinium iodide-MeI. The following (dialkylaminoalkoxy)alkylpiperidines were thus obtained (1-substituent, 2nd substituent, % yield, m.p. or b.p./mm. given): Me, 3-O-(CH₂)₂NMe₂, 11, 100-3°/9; Me, 3-O(CH₂)₂NMe₂ (di-MeI salt), 60, 294-7°; Et, 3-O(CH₂)₂NMe₂, 17, 102-6°/8; Me, 3-O(CH₂)₃NMe₂, 50, 142-4°/35; Me, 3-O(CH₂)₃-NMe₂ (di-MeI salt), 85, 214-16°; Me, 3-O(CH₂)₃NMe₂, (di-EtI salt), 71, 171-4°; Et, 3-O(CH₂)₃NMe₂, 38, 116-18°/6; Et, 3-O(CH₂)₃NMe₂ (di-MeI salt), 52, 197-200°; Me, 3-CH₂O(CH₂)₂NEt₂, 10, 113°/2; Et, 4-CH₂O(CH₂)₂-NEt₂, 40,106°/0.9; PhCH₂CH₂, 2-CH₂O(CH₂)₂NEt₂, 4, 120-4°/0.08.

Journal of Organic Chemistry published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C9H6ClNS, Computed Properties of 13444-24-1.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Buehler, C. A. published the artcilePhysiologically active compounds. II. Hydrochlorides of aminoesters of substituted benzilic and glycolic acids, Synthetic Route of 13444-24-1, the publication is Journal of Organic Chemistry (1958), 1432-7, database is CAplus.

cf. C.A. 51, 17843h. Aminoester hydrochlorides of 39 substituted benzilic and glycolic acids were synthesized; 2 of them appear to be more active in exptl. animals than atropine in preventing mortality from an anticholinesterase compound, and 4 of them exhibit the highest anticholinergic activity. One compound previously reported offers some advantage over these as an anticholinergic. β-Aminoethyl chlorides were prepared by the procedures given in the previous paper. Tetrahydrofurfuryl alc. with SOCl₂ gave 73% tetrahydrofurfuryl chloride (I). I, NHEt₃, and NaI gave 53% N,N-diethyltetrahydrofurfurylamine (II). II was converted by HBr to 80% N-ethyl-3-hydroxypiperidine (III). III with SOCl₂ gave N-ethyl-3-chloropiperidine-HCl which with aqueous NaOH gave the free N-ethyl-3-chloropiperidine. The following RR’C(OH)CO₂(CH₂)_xR”.HCl were prepared by refluxing the proper benzilic acid with the aminoethyl chloride in dry iso-PrOH (R, R’, R”, Χ, % yield, and m.p. given): 2-MeC₆H₄, 2-MeC₆H₄, N-ethyl-3-piperidyl (IV), 0, 69, 186-7°; 3-MeC₆H₄, 3-MeC₆H₄, N-ethyl-3-piperidyl, 0, 81, 150-1°; 4-iso-PrC₆H₄, 4-iso-PrC₆H₄, Et₄N, 2, 64, 181-2°; 2-MeOC₆H₄, 2-MeOC₆H₄, Et₂N, 2, 65, 171-2°; 4-MeOC₆H₄, 4-MeOC₆H₄, Et₂N, 2, 77, 167-8.5°; 4-MeOC₆H₄, 4-MeOC₆H₄, pyrrolidino, 2, 92, 181-2°; 4-MeOC₆H₄, 4-MeOC₆H₄, pyrrolidino (MeBr derivative), 2, 53, 147-8°; 2,3-(MeO)₂C₆H₃, 2,3-(MeO)₂C₆H₃, Et₂N (V), 2, 83, 184-5°; 3,4-(MeO)₂C₆H₃, 3,4-(MeO)₂C₆H₃, Et₂N, 2, 79, 167.5-8.5°; 3,4-methylenedioxyphenyl, Ph, Et₂N (VI), 2, 73, 164-5.5°; 3-PhC₆H₄, Ph, Et₂N, 2, 73, 136-7°; 3-PhC₆H₄, Ph, Et₂N (VII), 2, 60, 178-9°; 4-PhC₆H₄, Ph, piperidyl, 2, 70, 189-90°; 4-PhC₆H₄, Ph, N-ethyl-3-piperidyl (VIII), 0, 65, 149-50°; 3-PhC₆H₄, 3-PhC₆H₄, Et₂N (IX), 2, 59, 158-9°; 3-PhC₆H₄, 3-PhC₆H₄, piperidino, 2, 68, 197-8°; 4-PhC₆H₄, 4-PhC₆H₄, Et₂N, 2, 72, 183-5°; 4-PhC₆H₄, 4-PhC₆H₄, piperidino (X), 2, 47, 192-3°; 4-PhC₆H₄, 4-PhC₆H₄, N-ethyl-3-piperidyl (XI), 0, 74, 190-1°. 2-Phenylbenzilic acid could be prepared neither by an analogous procedure from 2-bromobiphenyl through the action of 2-biphenylmagnesium iodide on isonitrosoacetophenone nor through a mixed benzoin condensation of BzH and 2-PhC₆H₄CHO (XIa). The Grignard reagent of 3-bromobiphenyl (XII) reacted with N-methylformanilide to form 3-phenylbenzaldehyde (XIII) which was subjected to the benzoin condensation to give 3,3′-diphenylbenzoin (XIV). XIV was oxidized with CuSO₄ in C₅H₅N to the corresponding benzil (XV) which on rearrangement with KOH gave 3,3′-diphenylbenzilic acid (XVI). 2,2′-Diphenylbenzilic acid could not be produced because of the failure of XIa to undergo the benzoin condensation. XII and Et phenylglyoxylate (XVII) were prepared by known methods. XII (23.4 g.) in 300 ml. Et₂O added dropwise to 2.51 g. Mg and Et₂O under N, the solution refluxed 2 hrs., the Grignard solution added dropwise to 17.8 g. XVII in 200 ml. Et₂O, the solution refluxed 2 hrs., 250 ml. dilute HCl added, the Et₂O layer separated, the H₂O portion extracted with more Et₂O, the extracts combined, and distilled gave 18 g. Et 3-phenylbenzilate (XVIII), b₁ 213-18°. XVIII (18 g.) in 30 ml. alc. refluxed 3 hrs. with 20 g. KOH in 100 ml. H₂O, diluted with H₂O, acidified, and the precipitate collected gave 11 g. 3-phenylbenzilic acid, m. 127-8° (C₆H₆). XII (23.4 g.) in 250 ml. Et₂O treated with 2.51 g. Mg, then 13.5 g. N-methylformanilide added during 2 hrs., stirred 1 hr., decomposed, and separated gave 14 g. XIII, b₂ 138-44°; 2,4-dinitrophenylhydrazone, m. 234-5°. XIII (8 g.), 3 g. KCN, 40 ml. H₂O, and 80 ml. alc. refluxed. 10 hrs., cooled, diluted with H₂O, extracted with Et₂O, dried, and distilled gave 6 g. orange oil. This oil, 14 g. CuSO₄, 100 ml. C₅H₅N, and 30 ml. H₂O refluxed 6 hrs., the mixture poured onto ice and H₂O, the liquid decanted, and the solid dissolved in alc. gave 2.7 g. XV, m. 119-20° (MeOH); quinoxaline, m. 156°. XV (8 g.) in 300 ml. Et₂O left 24 hrs. with frequent shaking with 4 g. Na in 50 ml. 95% alc. and 25 ml. absolute alc., the solution extracted with H₂O, the aqueous solution extracted with Et₂O, heated to 90°, and acidified gave 3 g. crude XVI, m. 155-7° (C₆H₆). RR’C(OH)CO₂CH₂CH₂NEt₂.HCl (XIX) were prepared by dissolving 0.01 mole corresponding benzilate in AcOH, hydrogenating at 3 atm. over 0.1 g. Pt catalyst until reduction was complete, removing the catalyst and AcOH, and crystallizing the solid to give pure XIX. The following XIX were thus prepared (R, R’, % yield, and m.p. given): C₆H₁₁, C₆H₁₁, 72, 258-9°; C₆H₁₁, C₆H₁₁, 35, 212-13°; 2-MeC₆H₁₀, C₆H₁₁, 76, 165-6.5°; 3-MeC₆H₁₀, C₆H₁₁, 86, 181-2°; 4-MeC₆H₁₀, C₆H₁₁ (XX), 87, 190.5-2.0°; 2-MeC₆H₁₀, 2-MeC₆H₁₀, 80, 163.5-4.5°; 2,3-Me₂C₆H₉, C₆H₁₁, 79, 174-5°; 2,4-Me₂C₆H₉, C₆H₁₁, 79, 155-6°; 2,6-Me₂C₆H₉, C₆H₁₁, 81, 181-2°; 3,4-Me₂C₆H₉, C₆H₁₁, 80, 177.5-8.5°; 3,5-Me₂C₆H₉, C₆H₁₁, 73, 171.5-3.0°; 3-MeC₆H₁₀, 3-MeC₆H₁₀, 84, 178.5-9.5°; 4-MeC₆H₁₀, 4-MeC₆H₁₀, 82, 187-8°; 2,3,5-Me₃C₆H₈, C₆H₁₁, 76, 193-4°; 3,4,5-Me₃C₆H₈, C₆H₁₁ (XXI), 90, 216.5-18.0°; 3,5-Me₂C₆H₉, 3,5-Me₂C₆H₉, 84, 183-4°; 4-iso-PrC₆H₁₀, 4-iso-PrC₆H₁₀, 84, 185-7°; 3-C₆H₁₁C₆H₁₀, C₆H₁₁, 43, 133-4°; 4-C₆H₁₁C₆H₁₀, C₆H₁₁, 74, 174.5-5.5°; 2,3,6-Me₃C₆H₈, C₆H₁₁, 76, 199-200°. The above method was used to prepare all of the above XIX except with the di-C₆H₁₁ member in which the unreduced ester was prepared by the method of Hill and Holmes (U.S. 2,294,770) wherein the Me ester was refluxed with the appropriate amino alc. These compounds were tested for anticholinesterase activity, blood pressure, gut, respiration, and eye effects. VII and VIII appeared to be more active than atropine in preventing mortality from an anticholesterase compound The most active anticholinergic compounds are VI, XX, and XXI. VI and XXI are surpassed in activity by a previously prepared compound; this compound has much more marked effects on blood pressure and respiration than any of the 4 new compounds Compounds effective in dilating the pupil of the eye without significant irritant action are IV, V, VI, VIII, X, and XI. 3-PhC₆H₄CPh(OH)CO₂(CH₂)₂NEt₂.HCl and IX, which resemble V and VI in being diethylaminoethanol derivatives, are as active as the latter 2 compounds in dilating the pupil, but are definitely irritating.

Journal of Organic Chemistry published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C7H15NO, Synthetic Route of 13444-24-1.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Vilar, Santiago published the artcileProbabilistic Neural Network Model for the In Silico Evaluation of Anti-HIV Activity and Mechanism of Action, COA of Formula: C7H15NO, the publication is Journal of Medicinal Chemistry (2006), 49(3), 1118-1124, database is CAplus and MEDLINE.

A theor. model has been developed that discriminates between active and nonactive drugs against HIV-1 with four different mechanisms of action for the active drugs. The model was built up using a probabilistic neural network (PNN) algorithm and a database of 2720 compounds The model showed an overall accuracy of 97.34% in the training series, 85.12% in the selection series, and 84.78% in an external prediction series. The model not only correctly classified a very heterogeneous series of organic compounds but also discriminated between very similar active/nonactive chems. that belong to the same family of compounds More specifically, the model recognized 96.02% of nonactive compounds, 94.24% of active compounds that inhibited reverse transcriptase, 97.24% of protease inhibitors, 97.14% of virus uncoating inhibitors, and 90.32% of integrase inhibitors. The results indicate that this approach may represent a powerful tool for modeling large databases in QSAR with applications in medicinal chem.

Journal of Medicinal Chemistry published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C16H14O6, COA of Formula: C7H15NO.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Frawley, Thomas F. published the artcileAdrenal cortical function during isoniazid therapy for pulmonary tuberculosis, Application of 1-Ethylpiperidin-3-ol, the publication is American Review of Tuberculosis (1954), 841-51, database is CAplus.

The nature of the host’s response during isoniazid therapy for pulmonary tuberculosis suggested a possible adrenal cortical influence. By utilizing eosinophil levels, 17-keto steroid, uric acid, creatinine, and 17-hydroxy corticoid excretion patterns, the level of adrenal activity was determined before and during isoniazid therapy. Adrenal cortical responsiveness was assessed by the 8-hr. intravenous corticotropin test both before and during therapy. In no instance in either the resting or stimulated state was a significant or consistent deviation from the normal observed. A gradual rise in circulating eosinophils occurred during isoniazid therapy. The urinary uric acid-creatinine ratio varied directly with the disease progress and further use of this as an index of degree of disease activity is suggested.

American Review of Tuberculosis published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C7H15NO, Application of 1-Ethylpiperidin-3-ol.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Reynaud, Pierre published the artcileO-Dialkylaminoalkyl thioesters, analogs of adiphenine and related esters, Recommanded Product: 1-Ethylpiperidin-3-ol, the publication is European Journal of Medicinal Chemistry (1975), 10(3), 262-7, database is CAplus.

Imidates RCR1R2C(:NH)OEt [R = Ph, Pr; R1 = Ph, cyclopentyl, Pr; R2 = H; R1R2 = (CH2)4] reacted with H2S to give RCR1R2C(S)OEt; and transesterification of the latter yields eight resp. RCR1R2C(S)OR3 [R3 = CH2CH2NEt2, CH2CH2NMe2, 2-(1-piperidinyl)ethyl, 1-ethyl-3-piperidinyl], which demonstrated spasmolytic activity and were effective against induced tremor.

European Journal of Medicinal Chemistry published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C7H15NO, Recommanded Product: 1-Ethylpiperidin-3-ol.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Dalacroix, A. published the artcileUse of experience plans associated with direct methods for optimization in chemometry, Name: 1-Ethylpiperidin-3-ol, the publication is Analusis (1996), 24(1), M22-M25, database is CAplus.

Experience plans are discussed in connection with chemometry for statistical optimization of anal. methods and reaction processes, including methods for colorimetric dosing of ergotamine, the process of chlorination of ethyl-1-hydroxy-3-piperidine, generally spectrophotometric methods of anal., the process of urethane prepolymer synthesis, and the process of n-thymol synthesis by m-cresol alkylation.

Analusis published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C7H15NO, Name: 1-Ethylpiperidin-3-ol.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Fujimoto, James M. published the artcileBarbiturate metabolism as affected by certain agents acting on the liver, Name: 1-Ethylpiperidin-3-ol, the publication is Journal of Pharmacology and Experimental Therapeutics (1960), 139-43, database is CAplus and MEDLINE.

cf. Federation Proc. 17, 369(1958). N-Ethyl-3-piperidyl diphenylacetate (Dactil, JB-305) and benzilate (JB-371), N-methyl-3-piperidyl diphenylcarbamate (JB-371) (I), and β-phenylisopropylhydrazine (Catron, JB-516) (II) prolonged the sleeping time for certain barbiturates in mice, the effect varying with the particular barbiturate selected. Studies employing the whole-body concentration of hexobarbital, isolated rat liver perfusions, and measurements of bromsulfalein-retention point to effects of the prolonging agents on drug metabolites as a major factor in explaining the observed effects. In comparing the inhibitory spectrum of activity of these agents on drug metabolism I was found relatively most specific and II least specific.

Journal of Pharmacology and Experimental Therapeutics published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C7H15NO, Name: 1-Ethylpiperidin-3-ol.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem