反应详情

2-Amino-3-(4-cyano-3-fluoro-phenyl)-propionic acid ethyl ester. In a 1.0 L flask, a mixture of ethyl 2-(diphenylmethyleneamino)acetate (267 g, 1.0 mol) and the catalyst Bu4NBr (32 g, 0.1 mol) in CH3CN (1000 mL) was treated sequentially with 4-(bromomethyl)-2-fluorobenzonitrile (232 g) and K2CO3 (276 g, 2 mol). The mixture was then stirred for 24 hrs at room temperature. The mixture was filtered and concentrated to give ethyl 3-(4-cyano-3-fluorophenyl)-2-(diphenylmethyleneamino)propanoate (400 g, 100% yield) as a yellow oil. The crude was treated with 2M HCl (600 mL) in THF (400 mL) overnight, and then extracted with EtOAc (3×200 mL). The water phase was basified with a saturated Na2CO3 to pH 10 and extracted with EtOAc (3×200 mL). The combined organic layer was washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure to yield the title compound (153 g, yield 65% for the last three steps). The crude was not further purified and used straightly in next step.

1. filtrationThe mixture was filtered
2. concentrationconcentrated