反应详情

To a solution of N-[(3RS,4SR)-4-(3,4-dichloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-4-methoxy-N-methyl-3-trifluoromethyl-benzamide (50 mg, 0.090 mmol) in dichloromethane (1 mL) was added 3-bromopropionitrile (11 μL, 0.13 mmol) and an aqueous saturated solution of sodium carbonate (1000 μL). The resulting suspension was stirred for 18 h at ambient temperature. After the addition of dichloromethane (1 mL) and further 3-bromopropionitrile (11 μL, 0.13 mmol) it was stirred for 6 h at 40° C. After diluting with ethyl acetate (10 mL) the mixture was washed with an aqueous solution of sodium carbonate (10 mL) and water (10 mL). The aqueous layer was extracted with ethyl acetate (10 mL) and the combined organic layers were dried over sodium sulfate. Purification by chromatography (SiO2, heptane:ethyl acetate:(ethyl acetate:triethylamine=95:5):methanol=20:80:0:0 to 0:0:90:10) afforded the title compound (51 mg, 93%) as an light brown foam. MS m/e: 611.2 [M]+.

1. stirringwas stirred for 6 h at 40° C
2. washwas washed with an aqueous solution of sodium carbonate (10 mL) and water (10 mL)
3. extractionThe aqueous layer was extracted with ethyl acetate (10 mL)
4. dry with materialthe combined organic layers were dried over sodium sulfate
5. customPurification by chromatography (SiO2, heptane:ethyl acetate:(ethyl acetate:triethylamine=95:5):methanol=20:80:0:0 to 0:0:90:10)