反应详情

温度

0 °C

To a solution of tert-butyl [(1S)-1-(4-bromophenyl)ethyl]carbamate from Example 1, Step 7 (91.7 g, 305 mmol) in THF (1.5 L)/ether (300 mL) at −20° C. was added methyllithium (1.6M in ether, 229 mL, 366 mmol) and the mixture was slowly warmed to 0° C. and stirred for 30 min. and then cooled to −72° C. (internal temperature). n-Butyllithium (2.5M in hexanes, 146 mL, 366 mmol) was added dropwise and the mixture was stirred at −72° C. for 30 min. Excess CO2 gas was bubbled into the reaction mixture (white solid formation) and the suspension was allowed to warm in air for 30 min. and then to it was added 18 mL of acetic acid. The slurry was stirred at r.t. for 1 h and then filtered. The solid was collected and redissolved in acetic acid (50 mL), ethyl acetate and water and extracted with ethyl acetate. The organic layers were washed with water, dried over Na2SO4 and filtered. The crude product was washed with ether and dried under vacuum to give the desired product.

1. temperaturecooled to −72° C. (internal temperature)
2. stirringthe mixture was stirred at −72° C. for 30 min
3. customExcess CO2 gas was bubbled into the reaction mixture (white solid formation)
4. temperatureto warm in air for 30 min.
5. additionto it was added 18 mL of acetic acid
6. stirringThe slurry was stirred at r.t. for 1 h
7. filtrationfiltered
8. customThe solid was collected
9. dissolutionredissolved in acetic acid (50 mL)
10. extractionethyl acetate and water and extracted with ethyl acetate
11. washThe organic layers were washed with water
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. washThe crude product was washed with ether
15. customdried under vacuum