Oxalyl chloride → 3,3,3-Trifluoro-N-methoxy-N,2,2-trimethylpropanamide

Participants

Reaction Conditions

Reaction Steps

A 100 mL flask was charged with 3,3,3-trifluoro-2,2-dimethylpropanoic acid (1.00 g, 6.41 mmol), methylene chloride (25 mL) and DMF (1 drop). The system was purged with nitrogen and cooled to 0° C. Oxalyl chloride (0.650 mL, 7.69 mmol) was added dropwise over about 1 minute and the reaction was stirred at 0° C. for 2 min, then allowed to warm to room temperature. After 4 hours, a solution of N,O-dimethylhydroxylamine hydrochloride (0.937 g, 9.61 mmol) and N,N-diisopropylethylamine (3.35 mL, 19.2 mmol) in methylene chloride (5 mL) was added to the resulting acid chloride and the mixture was stirred at room temperature for 1 hour. The mixture was diluted with ether (50 mL) and washed with 1 M NaH2PO4 (2×15 mL), saturated NaHCO3 (15 mL), dried (Na2SO4), filtered and evaporated to obtain the amide as an oil (1.38 g, quant.), which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) 3.70 (s, 3H), 3.21 (s, 3H), 1.50 (s, 6H); m/z=200.3 (M+H)+.

Provenance & Evidence