Shapiro, Seymour L.’s team published research in Journal of the American Chemical Society in 81 | CAS: 13444-24-1

Shapiro, Seymour L. published the artcile3-Oxypiperidine derivatives, Formula: C7H15NO, the publication is Journal of the American Chemical Society (1959), 5146-9, database is CAplus.

cf. preceding abstract. The 3-oxypyridyl betaines and bis(3-oxypyridyl) betaines described in the preceding abstract hydrogenated over Rh-C yield the corresponding N-substituted-3-hydroxypiperidines and N,N’-bis(3-hydroxypiperidines), resp. These compounds, their ethers, and quaternary salts were examined for pharmacol. activity. N-(p-Chlorobenzyl)-3-oxypyridyl betaine-HCl (38.4 g.) in 250 cc. MeOH hydrogenated, 4 hrs. at 20° and 50 lb. initial pressure over 2 g. Rh-C, filtered, diluted with 300 cc. Et₂O, and the precipitate filtered off, the filtrate concentrated to 125 cc. and diluted with 260 cc. Et₂O, the precipitate filtered off, and the combined product (32.5 g.) recrystallized from MeOH-EtOAc yielded N-(p-chlorobenzyl)-3-hydroxypiperidine-HCl, m. 210-12°. Similarly were prepared the following compounds (m.p., % yield, and reduction time in hrs. given): 1-ethyl-3-hydroxypiperidine-HBr, 144-6° (EtOAc-Et₂O), 81, 1.75 [picrate, m. 81-3° (EtOAc-Et₂O)]; 1-benzyl-3-hydroxypiperidine-HCl, 167-70° (EtOH-EtOAc), 53, 4.5; 1-(2-dimethylaminoethyl)-3-hydroxypiperidine-2HCl, 267 8° (MeOH), 60, 1.5; 1-(3-dimethylaminopropyl)-3-hydroxypiperidine-2HCl (I), 222-6° (MeOH-EtOAc), 48. N-(5-Cyanopentyl)-3-oxypyridylbetaine-HCl (10.9 g.) in 200 cc. MeOH hydrogenated 9 hrs. over 2 g. Rh-C and filtered, the residue washed with 150 cc. H₂O, the MeOH removed from the combined filtrates, the aqueous residue basified with 6N NaOH, and the product isolated with CHCl₃ yielded 24% N-(6-aminohexyl)-3-hydroxypiperidine, b_0.08 110-12°, and 12% bis-[6-(3-hydroxypiperidino)hexyl]amine, b_0.2220-30°. 1-Phenacyl-3-oxypyridylbetaine-HCl(II)(40.8 g.) in 250 cc. MeOH hydrogenated over 2 g. Rh-C and worked up in the usual manner gave 5.0 g. distillate, b_0.09 90-5°, which deposited 0.4 g. 1-(2-phenethyl)-3-hydroxy-piperidine, m. 66-8° (hexane), and 22 g. 1-(2-hydroxy-2-phenylethyl)-3-hydroxypiperidine, b_0.05 140-50°. The p-Br derivative of II hydrogenated in the usual manner 16 hrs. yielded 8% 1-[2-(p-bromophenyl)-2-hydroxyethyl]-3-hydroxypiperidine (III), b_0.2 125-40°. The p-Cl derivative of II yielded similarly 6% p-Cl analog of III, m. 104-6° (heptane), and the p-Ph derivative of II gave 18% p-Ph (IIIa) analog of III, b_0.05 196-206°. The appropriate betaine hydrohalide (0.1 mole) in 250 cc. MeOH hydrogenated over 2 g. Rh-C gave the corresponding bis(3-hydroxypiperidino)alkane (m.p. or b.p./mm., % yield, and hydrogenation time in hrs. given): 1,3-bis(3-hydroxypiperidino)propane (IV), 146-51°/0.07, 50, 4, [dimethiodide m. 245-7° (EtOH)]; 1,4-butane analog (V) of IV, 108-10° (heptane), 60, 1, [V.2HCl, m. 263-5° (MeOH-EtOAc), 56%; V.2HBr, m. 261-5° (MeOH-EtOAc), 40%; V.2MeI, m. 235-7° (MeOH-EtOAc), 48%]; 1,5-pentane analog (VI) of IV, 176-80°/0.3, -, 6, (VI.2HBr, m. 173-5° (EtOH-EtOAc), 61%; VI.2MeI, m. 257-8° (EtOH), 73%); 1,6-hexane analog (VII) of IV, 91-3° (hexane), -, 5, [VII.2HBr, m. 219-21° (MeOH-EtOAc), 82%; VII.2MeI, m. 182-4° (EtOH), 71]; 1,4(1,4-dimethylbutane) analog, 162-8°/0.05, 59, 1.5; 1,10decane analog (VIII) of IV, 79-81° (pentane), -, 2, [VIII.-2HBr, 189-93° (MeOH-EtOAc), 33%; VIII.2MeI, m. 16575°]; p-CH₂C₆H₄CH₂ analog (IX) of IV, 140-3° (heptane), -, 7, [IX.2HCl, 309-10° (aqueous EtOH), 35%]. IV (3.9 g.) in 20 cc. C₅H₅N treated dropwise with stirring with 7.4 g. iso-PrCOCl during 0.5 hr., kept 20 hrs., and filtered, the residue dissolved in 15 cc. H₂O and 60 cc. Et₂O, the mixture adjusted to pH 8 with N NaOH and shaken, the aqueous phase extracted with 50 cc. Et₂O, and the combined Et₂O solutions worked up yielded 3.06 g. 1,3-bis(3-isobutyroxypiperidino)propane (X), b_0.03 156-8°. X (1.2 g.) in 8 cc. MeCN treated with 5 cc. p-MeC₆H₄SO₃Me, kept 10 days, and filtered yielded 0.2 g. X.2p-MeC₆H₄SO₃Me, m. 216-18° (MeOH). IV (10.5 g.) in 90 cc. PhMe treated at 50° with 2.54 g. NaH, refluxed 2 hrs. with stirring, the free base from 20.9 g. Me₂N-(CH₂)₂Cl.HCl in PhMe added, the mixture refluxed 20 hrs., cooled, and centrifuged, the supernatant decanted and evaporated, and the residue distilled yielded 7.86 g. 1,3-bis[3-(2-dimethylaminoethoxy)piperidino] propane, b_0.155 160-5°. VI.HBr (4.7 g.) in 49 cc. Ac₂O kept 6 days at 20°, the excess Ac₂O removed, the residue dissolved in 30 cc. Et₂O, the solution diluted with 15 cc. H₂O, adjusted with shaking with N NaOH to pH 8, the aqueous layer extracted with 25 cc. Et₂O, and the combined Et₂O solutions worked up yielded 1,5-bis(3-acetoxypiperidino)pentane (XI), b_0.05 158-64°. XI (177 mg.) in 5 cc. hexane treated with 1 cc. of a solution of 1.2 g. MeI in 10 cc. hexane, kept 4 days in the dark, and centrifuged, and the precipitate triturated with hexane gave XI.2MeI, hygroscopic, m. 108-13°. VIII (7.6 g.) in 100 cc. PhMe treated at 50° with 1.2 g. NaH, refluxed 2 hrs. with stirring, cooled, treated with 7.2 g. EtI, refluxed 3 hrs. with stirring, filtered, and distilled yielded 44% 1,10-bis(3-ethoxypiperidino)decane (XII), b_0.2 180-8°. N,N’-Tetramethylenebis(3oxypyridyl) betaine-2HCl (15.85 g.) in 250 cc. EtOH hydrogenated 9 hrs. over 0.5 g. PtO₂ and worked up in the usual manner yielded 4.5 g. 1,4-bis(piperidino)butane, b_0.05 114-20°, m. 107-10°; dipicrate, m. 189-90° (H₂O). N,N'(1,4-Buta-2-enylene)bis(3-oxypyridyl)betaine-2HBr hydrogenated 27 hrs. in the usual manner over PtO₂ and worked up gave 27 g. V, m. 108-12° (heptane). By the general procedures were prepared the following compounds XIII (R, Y, m.p./or b.p./mm., and % yield given): Ac, (CH₂)₃, 138-40°/0.05, 45; EtCO, (CH₂)₃ (XIV), 146-51°/0.03, 48; PrCO, (CH₂)₃, 156-62°/0.05, 57; Et, (CH₂)₃, 124°/0.02, 23; Ac, (CH₂)₄, 150-2°/0.02, 49; EtCO, (CH₂)₄ di-HCl salt, 270-5° (EtOH-hexane), 37; PrCO, (CH₂)₄, 170-4°/0.02, 58; iso-PrCO, (CH₂)₄, 156-62°/0.02, 34; Et, (CH₂)₄ (XV), 139-46°/0.1, 35; Me₂N(CH₂)₂, (CH₂)₄ (XVI), 148-65°/0.03, 21 [XVI.4MeI, m. 158-60° (EtOAc), 42%]; EtCO, (CH₂)₅ (XVII), 168-72°/0.04, 60; PrCO, (CH₂)₅ (XVIII), 177-84°/0.03, 550 iso-PrCO, (CH₂)₅, 178-88°/0.04, 50; Et, (CH₂)₅ (XIX), 140-50°/0.01, 34; Me₂N(CH₂)₂, (CH₂)₅, 168-75°/0.1, 34 [tetramethiodide, m. 250-4° (aqueous EtOH), 34%]; Ac, (CH₂)₆, 67-9° (aqueous Me₂CO), 8; EtCO, (CH₂)₆, 176-82°/0.03, 53; PrCO, 188-90°/0.03, 56; iso-PrCO, 180-5°/0.02, 88; p-O₂NC₆H₄CO, (CH₂)₆ dipicrate, 224-5° (BuOH), -; Et, (CH₂)₆ (XX), 150-8°/0.08, 29; Me₂NCH₂CH₂, (CH₂)₆ (XXI), 186-90°/0.16, 16 [XII.4MeI, m. 258-61° (MeOH-EtOAc), 20%]; Ac, CHMe(CH₂)₂CHMe (XXII), 158-62°/0.03, 81; Ac, (CH₂)₁₀, 76-8° (aqueous MeOH), 24; EtCO, (CH₂)₁₀ (XXIII), 196-204°/0.03, 64; PrCO, (CH₂)₁₀ (XXIV), 208-10°/0.08, 28 [XXIV.2p-MeC₆H₄SO₃Me, m. 125-7° (BuOH), 6%]; iso-PrCO, (CH₂)₁₀ (XXV), 198-208°/0.02, 34. Potentiated adrenaline activity was shown by I, IIIa, XIV, V.2HCl, XV, VI.2HBr, VI.2MeI, VII.2MeI, VIII.2HBr, moderate ganglionic blocking action by XVIII, partial block by IIIa, V.HCl, and XVI, adrenergic blocking effect by XXI and VIII.2HBr, and slight, lasting hypotensive effect by IIIa, V.HCl, XVI, and XIX. IIIa, LD_min. 750 mg./kg. subcutaneously, at 20 mg./kg. reduced the motor activity of rats 43%. XXI.4MeI showed depression of motor activity. Antiinflammatory activity of 17 units/g. was obtained with XII; XX, XXII, VI.2HBr, IV.2MeI, XV, XI, XVII, XIX showed lesser effectiveness. Curare-like effects (about 10% of the activity of decamethonium) were noted with XXI, XXIII, XXIV, XXV, and XII.

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 C25H23NO4, Formula: C7H15NO.

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