反应详情

4-Chlorobutyryl chloride (3.0 g) was added to a stirred, cooled solution of methyl (1aRS,7bSR)-5-[N-(methoxycarbonyl)-N-(2-amino-4-fluorobenzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (Intermediate 110, 0.135 g) and triethylamine (1.0 g) in THF (10 mL) at 0° C. On completion of the addition, the mixture was stirred at room temperature for 4 hours. Saturated aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and petroleum ether, with a gradient of 20-25% to give methyl (1aRS,7bSR)-5-{N-[methoxycarbonyl]-N-[2-(4-chlorobutyrylamino)-4-fluoro-benzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (0.15 g) as a yellow oil.

1. additionOn completion of the addition
2. extractionthe mixture was extracted with ethyl acetate
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. customThe filtrate was evaporated to dryness
6. customthe residue was purified by chromatography on silica
7. washeluting with a mixture of ethyl acetate and petroleum ether, with a gradient of 20-25%