反应详情

A mixture of methyl (1aR,7bS)-5-[2-((S)-1-ethylpyrrolidin-3-yloxymethyl)-4-fluorobenzene-sulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 213, 0.217 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, evaporated in vacuo and azeotroped with a mixture of toluene and ethanol. The residue was triturated with 15% methanol in DCM, filtered and the filtrate was evaporated in vacuo. The residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-20%. The resultant gum was triturated with ether and ethyl acetate and filtered to give (1aR,7bS)-5-[2-((S)-1-ethylpyrrolidin-3-yloxymethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.136 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. customazeotroped with a mixture of toluene and ethanol
5. customThe residue was triturated with 15% methanol in DCM
6. filtrationfiltered
7. customthe filtrate was evaporated in vacuo
8. customThe residue was purified by chromatography on silica
9. washeluting with a mixture of methanol and DCM with a gradient of 0-20%
10. customThe resultant gum was triturated with ether and ethyl acetate
11. filtrationfiltered