反应详情

温度

90 °C

A solution of affording trifluoro-methanesulfonic acid (2-cyano-3-methyl-5-morpholin-4-yl-phenyl)ester (0.43 g, 1.22 mmol), (3R)-3-fluoro-pyrrolidin (0.19 g, 1.47 mmol) and caesium carbonate (1.6 g, 4.92 mmol) in tetrahydrofuran (25 ml) is degassed and flushed with Argon for 30 min followed by the addition of palladium(II) acetate (6.0 mg, 0.03 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (23 mg, 0.04 mmol). The resulting mixture is stirred at 90° C. for 16 h. After completion of the reaction (monitored by TLC), the mixture is poured onto water (30 ml) and extracted with ethyl acetate (3×50 ml).The combined organic layers are washed with water (2×20 ml), brine (2×20 ml), dried over sodium sulfate and concentrated in vacuo. The crude product is purified by flash column chromatography (silica gel, 15% ethyl acetate/hexane) affording 2-[(3R)-3-fluoro-pyrrolidin-1-yl]-6-methyl-4-morpholin-4-yl-benzonitrile (0.18 g, 0.62 mmol, 50%).

1. customflushed with Argon for 30 min
2. customAfter completion of the reaction (monitored by TLC)
3. additionthe mixture is poured onto water (30 ml)
4. extractionextracted with ethyl acetate (3×50 ml).The combined organic layers
5. washare washed with water (2×20 ml), brine (2×20 ml)
6. dry with materialdried over sodium sulfate
7. concentrationconcentrated in vacuo
8. customThe crude product is purified by flash column chromatography (silica gel, 15% ethyl acetate/hexane)