A process for the formation of 2-(methyloxy)-N-[2-methyl-1-phenyl-2-(1-pyrrolidinyl)propyl]-4,6-bis(trifluoromethyl)benzamide is disclosed, comprising treatment of 2,4-ditrifluoromethyl-6-methoxy-benzoic acid with an arylsulphonyl halide, C
1-6
alkylsulphonyl halide or di-C
1-6
alkylphosphoryl chloride, in the presence of a base and an aprotic solvent; followed by reaction with [2-methyl-1-phenyl-2-(1-pyrrolidinyl)propyl]amine or a salt thereof. Also disclosed is a process for the formation of [2-methyl-1-phenyl-2-(1-pyrrolidinyl)propyl]amine comprising: i) treatment of an α-haloketone with an alcohol in the presence of a base followed by reaction with pyrrolidine; ii) treatment of the product of stage i) with Ar—CH(R
5
)N H
2
wherein R
5
is C
1-4
alkyl and Ar is optionally substituted phenyl, followed by reduction with a sodium borohydride derivative; and iii) reduction of the product of stage ii) with hydrogen and a palladium catalyst. Also disclosed is the novel compound 2-pyrrolidinyl-2-methylpropiophenone or a salt or solvate thereof.
本发明公开了一种制备2-(甲氧基)-N-[2-甲基-1-苯基-2-(1-
吡咯烷基)丙基]-4,6-双(三
氟甲基)苯甲酰胺的方法,包括在无
水溶剂中,在碱的存在下,用芳基磺
酰卤、C1-6烷基磺
酰卤或二C1-6烷基
磷酰
氯处理2,4-二三
氟甲基-6-
甲氧基苯甲酸,然后与[2-甲基-1-苯基-2-(1-
吡咯烷基)丙基]胺或其盐反应。本发明还公开了一种制备[2-甲基-1-苯基-2-(1-
吡咯烷基)丙基]胺的方法,包括:i) 在碱的存在下,用醇处理α-卤酮,然后与
吡咯烷反应;ii) 用Ar—CH(R5)NH2(其中R5为C1-4烷基,Ar为可选取代苯基)处理i)阶段的产物,随后用氢
硼酸钠衍
生物还原;以及iii) 用
氢气和
钯催化剂还原ii)阶段的产物。本发明还公开了新化合物2-
吡咯烷基-2-甲基
丙酮或其盐或溶剂。