反应详情

A mixture of methyl (1aRS,7bSR)-5-{2-[((S)-1-ethylpyrrolidin-3-ylcarbamoyl)methyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 80, 0.148 g) and lithium hydroxide monohydrate (0.168 g) in dioxane (3 mL) and water (1 mL) was irradiated in the microwave at 130° C. for 40 minutes. After cooling, the mixture was diluted with methanol, acidified with formic acid and evaporated in vacuo. The residue was triturated with 10% methanol in DCM and filtered. The filtrate was evaporated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-20%. The resultant solid was triturated with ether and filtered off to give (1aRS,7bSR)-5-{2-[((S)-1-ethylpyrrolidin-3-ylcarbamoyl)methyl]-4-fluorobenzenesulfonyl-amino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.091 g) as a white solid.

1. customwas irradiated in the microwave at 130° C. for 40 minutes
2. temperatureAfter cooling
3. customevaporated in vacuo
4. customThe residue was triturated with 10% methanol in DCM
5. filtrationfiltered
6. customThe filtrate was evaporated in vacuo
7. customthe residue was purified by chromatography on silica
8. washeluting with a mixture of methanol and DCM with a gradient of 0-20%
9. customThe resultant solid was triturated with ether
10. filtrationfiltered off