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目的:建立有效合成具有光活性的盐酸氟西汀中间体(R)-N,N-二甲基-2-羟基苯丙胺进而合成(R)-氟西汀的方法。方法:以[RuCl2((S)-BINAP)((S,S)-DPEN)]复合物为催化剂,在氢气压力为40bar下还原N,N-二甲基-1-苯丙酮,有效得到了具有光活性的重要中间体N,N-二甲基-2-羟基苯丙胺,合成了光活性的氟西汀。结果:反应在氢气压力为40 bar、反应温度为40℃、甲醇为溶剂、催化剂用量为0.05%(S/C=2 000)时,中间体的产率为84%,对映体过量百分比为93%,合成的总收率为49.1%,(R)-氟西汀对映体过量百分比为92%。结论:以[RuCl2((S)-BINAP)((S,S)-DPEN)]复合物为催化剂的体系能有效合成中间体(R)-N,N-二甲基-2-羟基苯丙胺,进而合成了具有光活性的(R)-氟西汀。
OBJECTIVE: To establish a method for the synthesis of (R) - fluoxetine, an effective intermediate of fluoxetine hydrochloride (R) -N, N-dimethyl-2-hydroxypropylamine hydrochloride. Methods: Reduction of N, N-dimethyl-1-propiophenone with [RuCl2 ((S) -BINAP) ((S, S) -DPEN)] complex under a hydrogen pressure of 40 bar gave An important intermediate of photo-activity, N, N-dimethyl-2-hydroxypropylamine, was synthesized and the photoactive fluoxetine was synthesized. Results: The reaction yield was 84% when the pressure of hydrogen was 40 bar, the reaction temperature was 40 ℃, the solvent of methanol was 0.05% (S / C = 2000) and the percentage of enantiomeric excess was 93%, the overall yield of the synthesis was 49.1%, and the enantiomeric excess of (R) -fluoxetine was 92%. CONCLUSION: The system of [RuCl2 ((S) -BINAP) ((S, S) -DPEN)] complex can effectively synthesize (R) -N, N-dimethyl- Further, the photoactive (R) -fluoxetine was synthesized.