New substituted tetrahydrofurans and process for preparing same

摘要

1,133,302. Substituted tetrahydrofurans. CIBA Ltd. 16 Jan., 1967 [19 Jan., 1966; 9 Dec., 1966], No. 2135/67. Heading C2C. Novel tetrahydrofurans that contain in the 2-position a phenyl or substituted phenyl and a piperidyl or pyridyl group, particularly compounds of the general formula wherein each of Ro, R1 and R11, which may be identical or different are C 1-6 alkyl, hydrogen, trifluoromethyl, halogen, or C 1-6 alkoxy, and R111 and Rx are C 1-6 alkyl or hydrogen and the corresponding compounds containing a pyridyl group attached to the 2-position of the tetrahydrofuran ring and the addition salts thereof, are prepared by reacting a 1-phenyl-1- pyridyl - 4 - (tert - amino) - 1 - butanol with an alkylating agent in the presence of a strong base and cyclizing the product to the desired pyridyl compound and hydrogenating this compound or a quaternary salt thereof to the corresponding piperidyl compound. The N- substituted piperidines of the above formula are also prepared by reacting N-unsubstituted compounds with a reactive ester of an alcohol to introduce an N-substituent, by N-acylating an N-unsubstituted piperidine and reducing the corresponding N-acyl compound, or by treating an N-unsubstituted compound with formaldehyde and formic acid to form an N-methyl compound. Racemic products may be resolved by normal methods. An N-aralkyl group may be removed by hydrogenolysis. 4 - (Dimethylamino) - 1 - phenyl (p - methyl-, p-methoxy-, and m- and p-chloro-phenyl)-1-(4- pyridyl)-1-butanol is obtained by reactingγ-dimethylaminopropyl magnesium chloride and the required 4-benzoyl-pyridine. By a similar method 4 - (dimethylamino) - 1 - phenyl - 1 - (2- and 3 - pyridyl) - 1 - butanol is prepared. 4-(p-Methoxybenzoyl)-pyridine is obtained from p - methoxyphenyl - magnesium bromide and 4-cyanopyridine. 2 - (p - Chlorophenyl) - 2 - (1 - acetyl - 4 - piperidyl)-tetrahydrofuran is prepared by reacting 2- (p - chlorophenyl) - 2 - (4 - piperidyl) - tetrahydrofuran with acetic anhydride. Therapeutic compositions, suitable for enteral or parenteral application, and incorporation into animal feedstuffs, contain the above novel piperidyl substituted tetrahydrofurans as the active ingredient. The compositions possess a wide range of pharmocological properties.