反应详情

To 3-(2,5-difluoro-benzenesulfonylamino)-2-fluoro-benzoic acid methyl ester (74, 0.955 g, 2.8 mmol) in 22 mL of tetrahydrofuran, lithium tetrahydroaluminate (6 mL, 1M in tetrahydrofuran, 6 mmol) is added at −40° C. under nitrogen. The reaction is allowed to warm to room temperature and stirred overnight. The reaction is poured into 1M aqueous sodium hydroxide, then neutralized with 1M aqueous hydrochloric acid. The solids are filtered through a bed of celite, and the celite bed is washed with ethyl acetate and tetrahydrofuran. The filtrate layers are separated and the aqueous layer is extracted with ethyl acetate. The organic layers are combined and washed with brine, dried over sodium sulfate, filtered and the filtrate is concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with ethyl acetate and dichloromethane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (75, 0.875 g). MS (ESI) [M−H+]−=316.

1. filtrationThe solids are filtered through a bed of celite
2. washthe celite bed is washed with ethyl acetate and tetrahydrofuran
3. customThe filtrate layers are separated
4. extractionthe aqueous layer is extracted with ethyl acetate
5. washwashed with brine
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationthe filtrate is concentrated under vacuum
9. customThe resulting material is purified by silica gel column chromatography
10. washeluting with ethyl acetate and dichloromethane
11. concentrationconcentrated under vacuum