反应详情

温度

-30 °C

To a cooled (−78° C.) solution of DIEA (4.9 mL, 48 mmol) in THF was added dropwise n-BuLi (132 mL, 2.3 eq, 2.5 M). The mixture was stirred at −30° C. for 30 min. Again the reaction mixture was cooled to −78° C., and a solution of 4-chloro-3-fluorobenzoic acid (25 g, 143 mmol) in THF was added over 1 h. The reaction was stirred at −78° C. overnight. The next day a solution of 1,2-dibromo-1,1,2,2-tetrachloroethane (87 g, 267 mmol) in THF was added and the reaction was stirred at −78° C. for further 2 h and then rt for 4 h. The reaction mixture was quenched with H2O, organic layer was separated and aqueous layer washed with Et2O. Aqueous layer acidified with 1.5 N HCl and extracted in EtOAc (2×200 mL), dried over anhydrous Na2SO4, filtered and concentrated to afford Intermediate 12A (30 g, 83.3%). MS (ESI) m/z: 252.6 (M−H)+.

1. temperatureAgain the reaction mixture was cooled to −78° C.
2. stirringThe reaction was stirred at −78° C. overnight
3. stirringthe reaction was stirred at −78° C. for further 2 h
4. waitrt for 4 h
5. customThe reaction mixture was quenched with H2O, organic layer
6. customwas separated
7. washaqueous layer washed with Et2O
8. extractionextracted in EtOAc (2×200 mL)
9. dry with materialdried over anhydrous Na2SO4
10. filtrationfiltered
11. concentrationconcentrated