反应详情

温度

0 °C

As per the procedures of WO2005058245, a solution of N-(phenylmethyl)-D-serine (79.51 g, 407.3 mmol) in THF (485 mL) was cooled to 0° C., and a precooled 0° C. solution of K2CO3 (168.87 g, 1222 mmol) in water (485 mL) was added. To the well-stirred mixture was added chloroacetyl chloride (45.4 mL, 570.0 mmol) slowly while keeping the internal temperature below 5° C. The mixture was vigorously stirred at 0° C. for 30 min, and then an additional portion of chloroacetyl chloride (4.54 mL, 57.0 mmol) was slowly added. The mixture was stirred for an additional 30 min at 0° C. To the mixture was added a sufficient quantity of precooled 0° C. aqueous NaOH (50% w/w) to adjust the pH>13.5 while keeping the internal temperature between 5° C. and 10° C. The mixture was stirred at 0° C. for 2 h, and then warmed to 20° C. The mixture was washed with heptane (165 mL) followed by a second portion of fresh heptane (240 mL). The aqueous phase was cooled to 0° C., and adjusted to pH<2 with concentrated aqueous HCl while keeping the internal temperature less than 10° C. The mixture was placed in a 0° C. freezer overnight, and the solid was collected by vacuum filtration. The solid was washed with water (2×300 mL) and dried in vacuo at 42° C. overnight. The resulting (3R)-5-oxo-4-(phenylmethyl)-3-morpholinecarboxylic acid (72.20 g, 75%) was isolated as a white solid. LCMS: (M+H)+: 236.1.

1. customthe internal temperature below 5° C
2. stirringThe mixture was stirred for an additional 30 min at 0° C
3. customthe internal temperature between 5° C. and 10° C
4. stirringThe mixture was stirred at 0° C. for 2 h
5. temperaturewarmed to 20° C
6. washThe mixture was washed with heptane (165 mL)
7. temperatureThe aqueous phase was cooled to 0° C.
8. customthe internal temperature less than 10° C
9. waitThe mixture was placed in a 0° C. freezer overnight
10. filtrationthe solid was collected by vacuum filtration
11. washThe solid was washed with water (2×300 mL)
12. customdried in vacuo at 42° C. overnight