4-Methylmorpholine → 5-Acetyl-N-methoxy-N-methylthiophene-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of 5-acetylthiophene-2-carboxylic acid (5 g, 0.0294 mol) in DMA (80 mL) was treated with EDCI (8.47 g, 0.044 mol), HOBt (3.97 g, 0.044 mol), N,O-dimethylhydroxylamine hydrochloride (5.7 g, 0.059 mol) and 4-methylmorpholine (16.14 mL, 0.147 mol). The resulting thick mixture was stirred at 25° C. for 16 h. Water (250 mL) was added and the mixture was extracted with 1:1 EtOAc/ether (2×200 mL). The combined extracts were washed with 1N HCl (150 mL), water (3×200 mL), saturated NaHCO3 (150 mL), and brine (150 mL); dried (Na2SO4); filtered; and evaporated to afford 5.4 g (86%) of the desired product. 1H NMR (300 MHz, DMSO-D6) δ ppm 2.58 (s, 3H) 3.31 (s, 3H) 3.78 (s, 3H) 7.85 (d, J=4.04 Hz, 1H) 7.92 (d, J=4.04 Hz, 1H); MS (DCI) 214 m/z (M+H)+.

Provenance & Evidence