反应详情

温度

-25 °C

A solution of 4-methylmorpholine (900 g) in THF (15 L) was added to 2-(tert-butoxycarbonylamino)propanoic acid (1690 g, 8933.17 mmol). The mixture was cooled to −25° C. and isobutyl chloroformate (1.164 L, 8933.17 mmol) was added. After 20 minutes the second equivalent of 4-methylmorpholine (900 g) was added followed by ethyl 2-amino-3-oxobutanoate Tosylate salt (see J-P. Genet et al, Eur. J. Org. Chem., 2004, 3017-3026) (2700 g, 8507.78 mmol) suspended in THF (2.5 L). The mixture was stirred at −25° C. for 30 minutes and then left to warm to ambient temperature overnight. The reaction was quenched with water (15 L), extracted with EtOAc (3×5 L) and the combined extracts washed with 50% saturated brine (5 L). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 50 to 80% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford ethyl 2-(2-(tert-butoxycarbonylamino)propanamido)-3-oxobutanoate (1850 g, 68.7%).

1. waitleft
2. temperatureto warm to ambient temperature overnight
3. customThe reaction was quenched with water (15 L)
4. extractionextracted with EtOAc (3×5 L)
5. washthe combined extracts washed with 50% saturated brine (5 L)
6. dry with materialThe organic layer was dried over MgSO4
7. filtrationfiltered
8. customevaporated
9. customto afford crude product
10. customThe crude product was purified by flash silica chromatography, elution gradient 50 to 80% EtOAc in isohexane
11. customPure fractions were evaporated to dryness