反应详情

To a −78° C. solution of 1-(3-chloro-4-fluorophenyl)ethanone (16.25 g, 94 mmol) and ethyl 2,2-diethoxyacetate (20.73 mL, 113 mmol) in THF (392 mL) was added, dropwise, a solution of LDA (51.8 mL, 104 mmol, 2M in THF). The resultant reaction mixture was gradually allowed to reach room temperature and continued stirring for 16 h. The reaction was carefully quenched with water and diluted with EtOAc. The two layers were separated and the aq. layer was extracted with EtOAc (2×150 mL) The combined organic layer was washed with brine, dried over anhydrous MgSO4, filtered and the filtrate was concentrated under reduced pressure to provide a crude oil. It was purified by silica gel chromatography (1500 g Commodity column, eluting with a 10% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate A39A (9.97 g, 35%) as a solid. MS(ES): m/z=257 [M-OEt]+.

1. customThe resultant reaction mixture
2. customto reach room temperature
3. customThe reaction was carefully quenched with water
4. additiondiluted with EtOAc
5. customThe two layers were separated
6. extractionthe aq. layer was extracted with EtOAc (2×150 mL) The combined organic layer
7. washwas washed with brine
8. dry with materialdried over anhydrous MgSO4
9. filtrationfiltered
10. concentrationthe filtrate was concentrated under reduced pressure
11. customto provide a crude oil
12. customIt was purified by silica gel chromatography (1500 g Commodity column
13. washeluting with a 10% EtOAc in hexanes)
14. additionFractions containing the product
15. customevaporated
16. customto afford Intermediate A39A (9.97 g, 35%) as a solid