反应详情

To a mixture of (S)-2-amino-4,4-difluoro-5-phenyl-pentanoic acid methyl ester hydrochloride (2.50 g, 8.94 mmol) and diisopropyl amine (22.3 mmol, 2.89 g) in dry dichloromethane (40 mL) under N2 is added drop wise morpholine carbonyl chloride (13.4 mmol, 2.0 g). The mixture is stirred at room temperature for 15 hours, and then diluted with water (50 mL). The aqueous layer is extracted with dichloromethane (30 mL). The organic layers are dried over magnesium sulfate and then concentrated in vacuum. Purification over 110 g silica gel, eluting with EtOAc:Heptane (1:1, then 2:1) affords (S)-4,4-difluoro-2-[(morpholine-4-carbonyl)-amino]-5-phenyl-pentanoic acid methyl ester (2.82 g, 88.5%).

1. extractionThe aqueous layer is extracted with dichloromethane (30 mL)
2. dry with materialThe organic layers are dried over magnesium sulfate
3. concentrationconcentrated in vacuum
4. customPurification over 110 g silica gel
5. washeluting with EtOAc:Heptane (1:1