PREPARATION PROCESS OF NOVEL BIPHENYLOXY-DERIVATIVES

摘要

1501541 Biphenyloxy derivatives DR KARL THOMAE GmbH 8 Jan 1976 [9 Jan 1975 25 Oct 1975] 00669/76 Heading C2C Novel compounds I: in which R 1 is C 1-6 alkyl, C 3-6 cycloalkyl, phenyl optionally substituted by 1 to 3 of halogen, C 1-3 alky and C 1-3 alkoxy, phenylalkyl, phenylalkenyl or pyridyl, R 2 is H or C 1-4 alkyl, R 3 is CH 2 OH, COOH, C 2-7 alkoxycarbonyl or C 4-8 cycloalkoxycarbonyl, A is -CONH- or -NHCO- and n is 1, 2 or 3, and, when R 3 is COOH, the salts thereof, are prepared by (a) reacting a compound II with a compound of formula where X is halogen, or (b) reacting a compound IV in which Y is an anion of an inorganic acid, with a compound V and, if desired, hydrolysing a resulting ester to the free acid. Compounds I in which R 3 is CH 2 OH are also prepared by reducing a compound I in which R 3 is other than CH 2 OH. Compounds II are prepared by reaction of appropriate amines with appropriate acids or derivatives thereof. Compounds VI are prepared from compounds IX in which R 4 is C 1-3 alkyl, by reduction followed by hydrolysis or by simultaneous ether clearage and hydrolysis, or from compounds X in which R 5 is H or C 1-3 alkyl; by reduction followed if required, by ether cleavage. 4-Aminomethyl- 41-hydroxy-biphenyl is also prepared by ether cleavage and hydrolysis of 4-methoxy-41-methoxycarbonylaminomethyl-biphenyl. The following intermediates are prepared in the examples: ethyl (4-methoxybiphenyl-41-yl)- ethanol, ethyl (4 - methoxybiphenyl - 41 - yl) acetate, 2 - (4 - methoxybiphenyl - 41 - yl) ethyl chloride, N - [2 - (4 - methoxybiphenyl - 41 - yl)- ethyl] phthalimide, 4 - methohy - 41 - methoxycarbonylaminomethyl - biphenyl, 4 - methoxy - 41- hydrazinocarbonylmethyl - biphenyl and 4 - (2- cyanoethyl) - 41 - methoxy - biphenyl. Pharmaceutical compositions having a cholesterol and triglyceride level lowering activity, for oral, rectal or parenteral administration, comprise a compound I together with a pharmaceutical carrier.