Method for preparing 4-ar3-1 (- 4-ar-4-ar2-butyl-4-hydroxypiperidine) and products obtained therefrom

摘要

1294733 4 - Phenyl - 1 - (4,4 - diphenylbutyl)- 4-hydroxy-piperidines JANSSEN PHARMACEUTICA NV 19 Aug 1970 [3 Sept 1969] 39975/70 Heading C2C Novel 4 - phenyl - 1 - (4,4 - diphenylbutyl). 4-hydroxy-piperidines of the general formula wherein R is a hydrogen atom or a methyl group, Ar 1 is a halophenyl group, Ar 2 is a phenyl or halophenyl group and Ar 3 is a phenyl, C 1-5 alkyl-phenyl, trifluoromethyl-phenyl, halophenyl, dihalophehyl, C 1-5 alkyl-halophenyl or trifluoromethyl-halophenyl group, and therapeutically acceptable acid addition salts thereof are prepared by heating a reactive ester of a 4,4- diphenyl-butan-1-ol of the general formula Ar 1 Ar 2 CH(CH 2 ) 3 OH with a 4-phenyl-4-hydroxypiperidine of the general formula followed optionally by salification of the product. 4-Phenyl-4-hydroxypiperidines of the third general formula above are prepared by condensing a 1-alkoxycarbonyl-4-oxo-piperidine of the general formula with a phenyl magnesium bromide of the general formula BrMgAr 3 under Grignard conditions and heating the resulting 1-alkoxycarbonyl-4-phenyl-4-hydroxypiperidine of the general formula with an alkali. Methyl 3-methyl-4-oxo-1-piperidine-carboxylate is prepared by reacting dimethyl 3,3SP1/SP-(benzyl-imino)-dipropionate and methyl chloroformate, cyclizing the resulting methyl N,N - bis - [2 - (methoxycarbonyl)ethyl] - carbamate in the presence of sodium methoxide, reacting the dimethyl 4-oxo-1,3-piperidinedicarboxylate so obtained with methyl iodide in the presence of sodium hydride and heating the resulting dimethyl 3-methyl-4-oxo-1,3-piperidinedicarboxylate with aqueous oxalic acid. 4,4- Diphenyl-butan-1-yl chlorides of the general formula Ar 1 Ar 2 CH(CH 2 ) 3 Cl are prepared by hydrogenating a 4-chloro-1,1-diphenyl-1-butene of the general formula Ar 1 Ar 2 C = CH(CH 2 ) 2 Cl in the presence of palladium. Pharmaceutical compositions having central nervous system depressant activity comprise, as active ingredient, a 4-phenyl-1-(4,4-diphenylbutyl)-4-hydroxy-piperidine of the first general formula above or a therapeutically acceptable acid addition salt thereof, in admixture with a therapeutically acceptable carrier therefor.