(R)-2-(2,5-difluorophenyl)pyrrolidine, preparation method and applications thereof

The invention discloses (R)-2-(2,5-difluorophenyl)pyrrolidine, a preparation method and applications thereof. The preparation method comprises: carrying out a hydrogenation reduction reaction on 5-(2,5-difluorophenyl)-3,4-dihydro-2H-pyrrole in the presence of imine reductase and reduced coenzyme NADPH to obtain the product. According to the invention, the ee value of the prepared (R)-2-(2,5-difluorophenyl)pyrrolidine can at least reach 94%, and the conversion rate can at least reach 84% through HPLC detection; the industrial production requirements of (R)-2-(2,5-difluorophenyl)pyrrolidine andlarotrectinib are met; and compared with the chemical method, the preparation method of the invention is low in cost and environment-friendly. 本发明公开了一种(R)-2-(2,5-二氟苯基)吡咯烷及其制备方法和应用。所述的制备方法包括：在亚胺还原酶和还原型辅酶NADPH的存在下，将5-(2,5-二氟苯基)-3,4-二氢-2H-吡咯进行加氢还原反应，即可。利用本发明的制备方法制备得到的R型的2-(2,5-二氟苯基)吡咯烷，ee值至少可达94％，通过HPLC检测转化率至少可达84％；满足了(R)-2-(2,5-二氟苯基)吡咯烷和larotrectinib的工业化生产需求；且本发明制备方法比化学方法成本更低，环境更加友好。