反应详情

Lithium hydroxide (0.22 g) was added to a solution of methyl (1aR,7bS)-5-{2-[2-((R)-1-ethyl-pyrrolidin-2-yl)ethyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (Intermediate 229, 0.26 g) in a mixture of dioxane (12 mL) and water (4 mL) and the mixture was irradiated in a microwave at 150° C. for 20 minutes. After cooling, the mixture was evaporated to dryness and the residue was acidified by addition of 10% aqueous citric acid (3 mL) and then extracted with DCM. The organic layer was dried (MgSO4) and filtered and the filtrate was evaporated to dryness. The residue was purified by preparative HPLC (C18) eluting with a mixture of acetonitrile and water, containing 0.1% formic acid, with a gradient of 25-35% to give (1aR,7bS)-5-{2-[2-((R)-1-ethylpyrrolidin-2-yl)ethyl]-4-fluoro-benzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.11 g) as a white solid.

1. customthe mixture was irradiated in a microwave at 150° C. for 20 minutes
2. temperatureAfter cooling
3. customthe mixture was evaporated to dryness
4. additionthe residue was acidified by addition of 10% aqueous citric acid (3 mL)
5. extractionextracted with DCM
6. dry with materialThe organic layer was dried (MgSO4)
7. filtrationfiltered
8. customthe filtrate was evaporated to dryness
9. customThe residue was purified by preparative HPLC (C18)
10. washeluting with a mixture of acetonitrile and water
11. additioncontaining 0.1% formic acid