反应详情

A mixture of methyl (1aRS,7bSR)-5-{2-[((S)-1-ethylpyrrolidin-2-yl)cabonylaminomethyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (Intermediate 101, 0.212 g) and lithium hydroxide (0.05 g) in dioxane (5.5 mL) and water (2.5 mL) was irradiated in the microwave at 150° C. for 30 minutes. After cooling, the mixture was diluted with water, acidified with formic acid to pH5 and extracted with ethyl acetate. The organic layer was washed with water, dried (MgSO4) and filtered. The filtrate was evaporate to dryness and the residue was purified by HPLC (C18) eluting with a mixture of methanol and water, containing 0.1% formic acid, with a gradient of 35-75% to give (1aRS,7bSR)-5-{2-[((S)-1-ethylpyrrolidin-2-yl)cabonylaminomethyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid (0.064 g) as a white solid.

1. customwas irradiated in the microwave at 150° C. for 30 minutes
2. temperatureAfter cooling
3. extractionextracted with ethyl acetate
4. washThe organic layer was washed with water
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. customThe filtrate was evaporate to dryness
8. customthe residue was purified by HPLC (C18)
9. washeluting with a mixture of methanol and water
10. additioncontaining 0.1% formic acid