Lithium Hydroxide → cis-(1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl cis-(1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluoro-benzenesulfonylmethyl]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 1, 0.72 g) and lithium hydroxide (0.622 g) in dioxane (20 mL) and water (5 mL) was stirred and heated at 80° C. for 5 hours. After cooling, the mixture was filtered and the filtrate was concentrated to low volume under vacuum. The aqueous residue was acidified with formic acid to pH 5 and extracted with DCM. The organic layer was dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by reverse phase chromatography using a C-18 5 micron cartridge and eluting with a mixture of methanol and water, with a gradient of 10-98%. The product was repurified by HPLC(C18) eluting with a mixture of acetonitrile and water (containing 0.1% formic acid) to give cis-(1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.125 g) as a white solid.

Provenance & Evidence