Dimethyl Sulfoxide → 4-Oxo-1-[4-(3-pyrrolidin-1-ylpropoxy)-phenyl]-cyclohexanecarbonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-cyano-2-oxo-5-[4-(3-pyrrolidin-1-ylpropoxy)-phenyl]-cyclohexanecarboxylic acid methyl ester (6.6 g, 17 mmol) and dimethylsulfoxide (128 mL) was added water (8.0 mL) and sodium chloride (6.4 g, 109 mmol). The reaction mixture was heated to 142-146° C. After 5 hr, the mixture was concentrated and the residue was dissolved in DCM (120 mL), washed with water (100 mL), and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (70 g silica gel, eluant:gradient of DCM/MeOH 95/5 to 90/10) providing 4-oxo-1-[4-(3-pyrrolidin-1-ylpropoxy)-phenyl]-cyclohexanecarbonitrile as a crystallizing oil (2.2 g, 45.5%). After crystallization in ether, 0.2 g of analytical sample were obtained. 1H NMR (400 MHz, CDCl3) δ7.32 (d, 2H), 6.88 (d, 2H), 4.1 (t, 2H), 2.95-2.8 (m, 2H), 2.65-2.38 (m, 10H), 2.3-2.15 (m, 2H), 2.0-1.9 (m, 2H), 1.8-1.7 (m, 4H).

Provenance & Evidence