反应详情

温度

-20 °C

To a suspension of (R)-2-acetylamino-3-methoxypropionic acid (5 g, 31.05 mmol) in tetrahydrofuran (50 mL), under a nitrogen atmosphere at −20° C., was added isobutyl chloroformate (4.04 mL, 31.05 mmol) over a period of 10 minutes. The temperature was maintained at −20° C. for 10 minutes. 4-Methylmorpholine (3.42 mL, 31.05 mmol) was added over a period of 10 minutes, and the temperature was maintained for a further 10 minutes. Benzylamine (3.39 mL, 31.05 mmol) was added directly into the reaction mixture via a syringe at −20° C. over a period of 10 minutes. The temperature of the reaction mixture was maintained at −20° C. for a further 20 minutes. The reaction mixture was quenched with aqueous HCl (1M; 21.88 mL). Solvent was removed by evaporation at 45-50° C., and crude material (16 g) was isolated. Ethyl acetate (50 mL) was added, and the reaction mixture was washed with water (2×2.5 mL). The organic layer was dried over sodium sulphate and the solvent was completely removed by evaporation to give crude material (5.77 g). A portion (5.5 g) of this material was dissolved in ethyl acetate (50 mL) at 50-55° C. The temperature was maintained for 10 minutes, before cooling to 25° C. After stirring at this temperature for 2 hours the reaction mixture was filtered. The wet filter cake was washed with ethyl acetate (2.5 mL). The residue was dried under suction for 20 minutes, then dried under vacuum at 40° C. to constant weight, to give the title compound (1.38 g, 18.5%). Chiral purity: 99.2%. Chemical HPLC: 96.8%.

1. temperaturethe temperature was maintained for a further 10 minutes
2. temperatureThe temperature of the reaction mixture was maintained at −20° C. for a further 20 minutes
3. customThe reaction mixture was quenched with aqueous HCl (1M; 21.88 mL)
4. customSolvent was removed by evaporation at 45-50° C.
5. customcrude material (16 g) was isolated
6. washthe reaction mixture was washed with water (2×2.5 mL)
7. dry with materialThe organic layer was dried over sodium sulphate
8. customthe solvent was completely removed by evaporation
9. customto give crude material (5.77 g)
10. temperatureThe temperature was maintained for 10 minutes
11. temperaturebefore cooling to 25° C
12. filtrationwas filtered
13. washThe wet filter cake was washed with ethyl acetate (2.5 mL)
14. customThe residue was dried under suction for 20 minutes
15. customdried under vacuum at 40° C. to constant weight