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PROCEDURE FOR PREPARATION OF N-METHYL-3-(P-TRIFLUOROMETHYLPHENOXY)-3-PHENYL-PROPYLAMINE HYDROCHLORIDE

机译:N-甲基-3-(对-三氟甲苯氧基)-3-苯基丙胺盐酸盐的制备方法

摘要

An improved process for the preparation of a valuable drug. The present invention relates to an improved process for the preparation of N-methyl-3-(p-trifluoromethylphenoxy)-3-phenyl-propylamine of formula (I), CHEM or a pharmaceutically acceptable acid addition salt thereof, characterized in that 2-benzoyl-N-benzyl-N-methylethylamine base of formula (II), CHEM is hydrogenated catalytically, whereby 1-phenyl-3-(N-methylamino)propane-1-ol of formula (III) is formed, CHEM which is thereafter etherified selectively with 1-chloro-4-trifluoromethylbenzene of formula (IV), CHEM in the presence of a base, whereby N-methyl-3-(p-trifluoromethylphenoxy)-3-phenyl-propylamine is formed, which is optionally converted in a known manner into the acid addition salt of Fluoxetine, e.g. Fluoxetine hydrochloride. The yield of Fluoxetine hydrochloride is 85-87% of the theoretical yield.
机译:一种制备有价值药物的改进方法。本发明涉及一种改进的制备式(I)的N-甲基-3-(对-三氟甲基苯氧基)-3-苯基-丙胺或其药学上可接受的酸加成盐的方法,其特征在于将式(II)的2-苯甲酰基-N-苄基-N-甲基乙基胺碱催化氢化,由此形成式(III)的1-苯基-3-(N-甲基氨基)丙烷-1-醇,然后在碱的存在下用式(IV)的1-氯-4-三氟甲基苯将选择性地醚化,,由此得到N-甲基-3-(对三氟甲基苯氧基)-3-苯基丙胺形成氟,其任选地以已知方式转化为氟西汀的酸加成盐,例如盐酸氟西汀。盐酸氟西汀的产率为理论产率的85-87%。

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