4-Methylmorpholine → N-[4-(Hydroxymethyl)phenyl]-N-methylacetamide

Participants

Reaction Conditions

Reaction Steps

An oven dried flask, under nitrogen flow, was charged with a stir bar, 4-(N-acetyl-N-methylamino)benzoic acid (1.0 g, 5.18 mmol), prepared as in step 7, anhydrous DME (10.3 mL), and anhydrous DMF (3.0 mL). The resulting solution was cooled to -20° C., and 4-methylmorpholine (0.60 mL, 5.4 mmol) and isobutyl chloroformate (0.70 mL, 5.4 mmol) were added sequentially via syringe. The reaction mixture was stirred under N2 at -20° C. for 1 hour. The resultant yellow mixture was filtered and the precipitate washed with DME (2×~1 mL). The combined flitrate and washings were cooled to 0° C. and sodium borohydride (800 mg, 21.1 mmol) dissolved in water (2.0 mL) was added dropwise. The reaction was stirred at 0° C. for 15 min. and quenched with saturated aqueous ammonium chloride. The resulting mixture was partitioned between ethyl acetate and brine. The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo to give an oil. Purification by flash chromatography on silica gel (90% ethyl acetate/hexane) provided 4-(N-acetyl-N-methylamino)benzyl alcohol as a colorless oil which solidified on standing. Recrystallization from hexane provided the alcohol as a colorless solid (543.0 mg, 58.5%). mp 83.5°-85.5° C. 1H NMR (300 MHz, CDCl3) δ 7.45 (2H, d, J=8.5 Hz), 7.18 (2H, d, J=8.5 Hz), 4.75 (2H, s), 3.27 (3H, s), 1.90 (3H, MS m/e 180 (M+H)+, 197 (M+NH4)+.

Provenance & Evidence