Methanol → 4-(4-fluorophenyl)-N-methylbutyramide

Participants

Reaction Conditions

Reaction Steps

At 0° C., 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (6.99 g, 36.5 mmol) was added to a solution of crude 4-(4-fluorophenyl)butyric acid (6.64 g, 36.5 mmol) and 1-hydroxybenzotriazole (4.92 g, 36.5 mmol) in N,N-dimethylformamide (50 ml) and DCM (50 ml). The reaction mixture was stirred for 20 min at 0° C. An 8.0 M solution of methylamine in methanol (91 ml. 729 mmol) was added. The reaction mixture was stirred for 16 hours, while it was warming up to room temperature. It was diluted with ethyl acetate (200 ml) and washed with a 10% aqueous solution of sodium hydrogen sulphate (100 ml). The aqueous phase was extracted with ethyl acetate (100 ml). The combined organic layers were washed with a saturated solution of sodium hydrogen carbonate (200 ml) and dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (100 g), using ethyl acetate/heptane 3:1 as eluent. The product was dissolved in ethyl acetate (200 ml) and washed with water (200 ml). The organic layer was dried over magnesium sulphate. The solvent was removed in vacuo to give 1.31 g of 4-(4-fluorophenyl)-N-methylbutyramide.

Provenance & Evidence