122334-36-5

N-Methoxy-N,4-dimethylbenzamide is used in the synthesis of Fingolimod (F342045)

GENERAL PROCEDURE: Methoxymethylamine (0.360 g, 6.0 mmol) and p-methylbenzoic acid (0.244 g, 2.0 mmol) were dissolved in anhydrous toluene (10 mL) and stirred for 10 min at 0 °C. Subsequently, a solution of phosphorus trichloride (0.137 g, 1.0 mmol) in anhydrous toluene (2 mL) was slowly added dropwise to the above mixture. The reaction mixture was gradually warmed up to room temperature, followed by stirring at 60 °C for 0.5 hours. The progress of the reaction was monitored by thin layer chromatography (TLC) and after confirming the completion of the reaction, the mixture was cooled to room temperature. The reaction was quenched with saturated sodium bicarbonate solution (20 mL) and extracted with ethyl acetate (3 x 10 mL). The organic layers were combined and dried over anhydrous magnesium sulfate. The solvent was removed by concentration under reduced pressure and the resulting crude product was purified by column chromatography (silica gel, petroleum ether-ethyl acetate, 3:2) to afford the colorless oily target product N-methoxy-N,4-dimethylbenzamide (320 mg, 97% yield).

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[2] Organic Letters, 2000, vol. 2, # 25, p. 4091 - 4093
[3] Chimia, 1995, vol. 49, # 10, p. 381 - 385