Najer, Henri published the artcileSpasmolytically active α-phenyl-α-tertiary-aminoacetates, Application of 1-Ethylpiperidin-3-ol, the publication is Bulletin de la Societe Chimique de France (1958), 355-9, database is CAplus.
cf. C.A. 52, 10073a. To assess their spasmolytic activity with respect to acetylcholine and BaCl2, beta;-tertiary-aminoethyl β-tertiary-aminoethoxyethyl α-phenyl-α-tertiary-aminoacetate dihydrochlorides, RPhCHCO2R1.2HCl (R1 = CH2CH2R2) (I) and (R1 =CH2CH2OCH2CH2R2) (II) were prepared Treatment of the appropriate alc in Et2O at 0° with PhCHClCOCl gave α-phenyl-α-chloroacetate HCl salts, PhCHClCO2R1.HCl (R1 = CH2CH2R2) (III), and (R1 = CH2CH2OCH2CH2R2) (IV). The unstable corresponding bases (V, VI) refluxed several hrs. in C6H6 with a suitable secondary amine gave the bases of I and II (VII, VIII). The toxicity (L.D.50 in mg./kg.) was determined by intravenous injection in white mice according to the method of Kaerber and Behrens. The spasmolytic activity on isolated guinea pig intestine against acetylcholine spasm and BaCl2 spasm was measured in comparison with Ph2CHCO2CH2CH2NEt2.HCl (IX) and papaverine hydrochloride (X), resp. Piperidine (76.5 g.) and 50 g. AcOCH2CH2OCH2CH2Cl in 75 ml. absolute alc. heated 18 hrs. in a sealed tube, the cooled solution evaporated in vacuo, the residue in 30 ml. H2O made alk. with 40 ml. 40% Na2CO3, the oily product extracted 4 times with 100 ml. Et2O, the dried extracts (Na2SO4) evaporated, the residual oil distilled gave 39.5 g. β-piperidinoethoxyethanol, b3 105-6°; HCl salt, m. 120° (Me2CO) (all m.ps. on Maquenne block). Similarly was prepared 70% β-morpholinoethoxyethanol, b3 106-8°; HCl salt, m. 157° (iso-PrOH). PhCHClCOCl (245 g.) in 1 l. anhydrous Et2O at 0° stirred 1 hr. with gradual addition of 151 g. Et2NCH2CH2OH in 800 ml. Et2O and the mixture kept 1 hr. at 0° and 24 hrs. at room temperature, filtered, and the Et2O-washed product air-dried gave III (R2 = NEt2) (IIIa). IIIa (357 g.) in 1 l. H2O adjusted to pH 9 with saturated aqueous Na2CO3 and the oily product extracted 4 times with 500 ml. Et2O gave 236 g. crude V (R2 = NEt2) (Va) suitable for immediate condensation with the appropriate secondary amine. PhCHClCOCl (48 g.) in 200 ml. Et2O at 0° stirred with gradual addition in 20 min. of 32 g. β-(1,2,5,6-tetrahydro-1-pyridyl)ethanol (cf. C., et al., loc. cit.) in 200 ml. Et2O and the mixture kept 30 min. at 0° and 24 hrs. at room temperature gave 50 g. oily III (R2 = NC5H9). Similarly were prepared the analogous hydrochlorides, III and IV (series, R2, m.p. (solvent), and % yield given): III, NEt2, 123° (iso-BuOH), 91; III, NC4H8O (= morpholino), 166° (iso-BuOH), 74; 3-(N-ethylpiperidinyl), 166° (iso-PrOH) (hygroscopic), 99; IV, NEt2, oil (-), -; IV, NC5H10 (= piperidino), 116° (AcEt), 98; IV, NC4H8O, 84° (EtOAc), 80. Va (56.4 g.) in 250 ml. dry C6H6 refluxed 8 hrs. with 34.8 g. 1,2,5,6-tetrahydropyridine, the cooled mixture filtered, the precipitated HCl salt washed repeatedly with dry C6H6, the filtrate and washings evaporated in vacuo, the residue in 200 ml. H2O extracted 3 times with 200 ml. Et2O and the dried extract evaporated gave VII (R = NC5H8, R2 = NEt2), converted in dry Et2O by passage of dry HCl to the corresponding I; di-HBr salt, m. 197-200° (iso-PrOH). Similarly were prepared the analogous bases VII, VIII and the corresponding di-HCl salts [series, R, R2, b.p./mm. and % yield of base, m.p. (solvent) of dihydrochlorides, toxicity (L.D.50), and spasmolytic activity in respect to acetylcholine and BaCl2 given]: I (Ia), NC5H10, NEt2, 163-4°/0.2, 68, 214-15° (alc.-Et2O), 55, 1.30, 0.9; I (Ib) NC5H10, NC5H10, 169-70°/0.4 79, 238° (iso-PrOH), 80, 2, 6; I, NC5H10, C7H14N (= 1-ethyl-3-piperidyl), 170-2°/0.5, 61, 235° (alc.-Et2O), 85, 0.2, 0.2; I, NC5H10, NC5H8, 180-2°/0.5, 90, 227-8° (iso-PrOH), 92, 0.8, 3; I, NC5H10, NC4H8O, 180-3°/0.09, 70, 195-200° (alc.-Et2O), 205, 0.02, 0.1; II, NC5H10, NEt2, 186-7°/0.4, 74, paste (-), 57, 0.75, 1.0; II, NC5H10, NC5H10, 190-2°/0.2, 45, 214° (iso-PrOH), 77, 0.10, 0.7; II, NC5H10, NC4H8O, 218-20°/1.0, 72, 211-12° (iso-PrOH), 210, 0.02, 0.2; I, 3-methylpiperidino, NEt2, 164-6°/0.5-0.6, 68, 227° (alc.-Et2O), 67.5, 0.25, 1.0; I, 3-methylpiperidino, NC5H10, 180-2°/0.6-0.8, 69, 229° (alc.-Et2O), 75, 0.40, 1.2; I, 3-methylpiperidino, C7H14N, 177/0.4, 64, 216° (alc.-Et2O), 90, 0.07, 1.0; I, 4-methylpiperidino, NEt2, 192-3°/3.0, 42, 225° (alc.-EtOAc), 80, 0.75, 6; I, 4-methylpiperidino, NC5H10, 185-7°/1.0, 67, 239° (alc.-Et2O), 70, 0.45, 1.0; I, 4-methylpiperidino, C7H14N, 168-9°/0.2, 61, 233° (alc.-Et2O), 80, 0.15, 0.8; I, NC5H8, NEt2, 167-70°/0.8-0.9, 69, hygroscopic (iso-PrOH-Et2O), 97, 1.0, 5.0; I, NC5H8, NC5H10, 215-18°/1.5, 49, 236° (iso-PrOH), 92.5, 1.0, 1.0; I, NC5H8, NC5H8, 189-90°/0.8, 70, 222-4° (iso-PrOH), 107, 0.5, 4.0; II, NC5H8, NEt2, 189-91°/0.3, 42, 161° (Me2CO), 55, 0.5, 1.0; II, NC5H8, NC5H10, 199-200°/0.5, 76, hygroscopic (-), 82, 0.05, 1.5; II, NC5H8, NC4H8O, 203-5°/0.2, 57, 198° (iso-PrOH), 285, 0.01, 0.4 I, NC4H8, NEt2, 138-40°/0.05, 60, 135-40° (hygroscopic), 117.5, 1.0, 1.3; I, NC4H8, NC5H10, 168-70°/0.5, 66, 218° (alc.-Et2O), 87.5, 1.0, 0.5; I, NC4H8, C7H14N, 160-2°/0.5, 70, hygroscopic (iso-PrOH-Et2O), 82.5, 0.05, 1.0; I, NC4H8O, NEt2, 154-6°/0.05-0.06, 56, 217° (AcEt-alc.), 275, 0.03, 0.9; I, NC4H8O, NC5H10, 174-6°/0.05, 36, 170-5° (hygroscopic), 138, 0.1, 0.1; I, NC4H8O, C7H14N, 170-4°/0.7, 60, 214° (iso-PrOH-Et2O), 180, less than 0.1, 0.2. In comparison, IX and X had L.D.50 42 and 30 and spasmolylic activities 1 against acetylcholine and 1 against BaCl2, resp. The compounds with most favorable spasmoltyic action are I in which R is piperidino or 1,2,5,6-tetrahydropyridyl, and whatever the nature of R the antiacetylcholenic action is greatest when R2 is NEt2 or piperidino. No particular conclusion was made as to the relation between the nature of R2 and the musculotropic activity against BaCl2. Ib had the most favorable activities of all the compounds examined and had a favorable therapeutic coefficient in comparison with IX and X.
Bulletin de la Societe Chimique de France 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