Dimethylformamide → 4-(4-Fluorophenyl)-4-hydroxycyclohexan-1-one

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Reaction Steps

To a solution of 21.65 g. (0.085 mole) of 4-hydroxy-4-(p-fluorophenyl)cyclohexanone dimethyl ketal (prepared as in Example 25) in 80 ml. of dimethylformamide and 320 ml. of benzene, 3.56 g. of 57% sodium hydride is added. Following about 1 hour of stirring at room temperature, 35 ml. of methyl iodide is added and the mixture heated at reflux. After about 4 hours of heating an additional 10 ml. of methyl iodide is added. At the end of about 18 hours of heating, the suspension, after cooling, is washed with water and brine. The organic layer is evaporated to dryness and the gum remaining dissolved in 400 ml. of acetone, then 40 ml. of 2.5N hydrochloric acid added. At the end of about 4 hours, most of the solvent is removed under vacuum. The residue is extracted with ether and the organic layer washed with aqueous sodium bicarbonate solution and brine and then evaporated to dryness. The residual gum is chromatographed on a 2 l. column of Florisil (synthetic magnesium silicate), with elution by 2 l. of Skellysolve B, 2 l. of 95% Skellysolve B:5% acetone and 4 l. of 70% Skellysolve B:30% acetone. Crystalline fractions of first the product, then 6.87 g. (49%) of 4-hydroxy-4-(p-fluorophenyl)-cyclohexanone, melting at 108° to 114° C., are obtained. The product is recrystallized from petroleum ether to give 7.76 g. (41%) of 4-methoxy-4-(p-fluorophenyl)cyclohexanone, melting at 60° to 69° C. The analytical sample melts at 68° to 70° C.

Provenance & Evidence