Hydrochloric Acid → Methyl 5-cyano-5-[3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl]-2-oxocyclohexanecarboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of dimethyl 4-cyano4-(3-cyclopentyloxy-4-difluoromethoxyphenyl)pimelate (3.1 g, 6.7 mmol) in dry 1,2-dimethoxyethane (50 mL) under an argon atmosphere was added sodium hydride (80% dispersion in mineral oil, 0.81 g, 27 mmol). The resulting mixture was refluxed for 20 min, additional 1,2-dimethoxyethane (50 mL) was added and the mixture was refluxed for another 70 min. The mixture was cooled to 0° C., was acidified with dilute hydrochloric acid and was concentrated The mixture was partitioned between ether and dilute hydrochloric acid, the organic layer was dried (magnesium sulfate) and the solvent was removed in vacuo. The product was purified by flash chromatography, eluting with 85:15 hexanes/ethyl acetate, to provide a white solid (0.76 g, 37%): m.p. 109°-110.5° C. Analysis Calc. for C21H23F2NO5 : C 61.91, H 5.69, N 3.44; found: C 61.83, H 5.66, N 3.39.

Provenance & Evidence