反应详情

温度

100 °C

Methyl (1aRS,7bSR)-5-(2-{[((S)-1-ethylpyrrolidine-3-carbonyl)amino]methyl}-4-fluoro-benzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 188, 0.190 g) and lithium hydroxide monohydrate (0.150 g) were suspended in dioxane (5 mL) and water (5 mL) and the mixture was stirred and heated at 100° C. for 18.5 hours. After cooling, the volatiles were removed in vacuo and the residue was acidified by addition of aqueous citric acid solution (10%) and extracted with DCM. The organic layer was dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and 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 25-60% to give (1aRS,7bSR)-5-(2-{[((S)-1-ethylpyrrolidine-3-carbonyl)amino]methyl}-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.092 g) as a white solid.

1. temperatureAfter cooling
2. customthe volatiles were removed in vacuo
3. additionthe residue was acidified by addition of aqueous citric acid solution (10%)
4. extractionextracted with DCM
5. dry with materialThe organic layer was dried (Na2SO4)
6. filtrationfiltered
7. customThe filtrate was evaporated to dryness
8. customthe residue was purified by preparative HPLC (C18)
9. washeluting with a mixture of acetonitrile and water
10. additioncontaining 0.1% formic acid