Triethylamine → 3,3,3-Trifluoro-N-methoxy-N,2,2-trimethylpropanamide

Participants

Reaction Steps

To a clear solution of 3,3,3-trifluoro-2,2-dimethylpropionic acid (5.000 g, 32.0 mmol) in MeCN (22.88 ml) was added triethylamine (9.82 ml, 70.5 mmol) followed by HATU (12.79 g, 33.6 mmol) and the mixture was stirred at room temperature. After 15 min, to the dark clear mixture was added N,O-dimethylhydroxylamine hydrochloride (3.44 g, 35.2 mmol) and the mixture was stirred at room temperature. After 18 h, the reaction mixture was diluted with EtOAc (100 mL) and washed with 1 N HCl (2×100 mL), and sat. NaCl (5×100 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a orange solid. The orange solid was absorbed onto a plug of silica gel and purified by silica gel chromatography eluting with a gradient of 0% to 25% EtOAc in heptane to provide 3,3,3-trifluoro-N-methoxy-N,2,2-trimethylpropanamide (5.0503 g, 25.4 mmol, 79% yield) as yellow liquid. 1H NMR (300 MHz, CDCl3) δ 3.71 (3H, s), 3.22 (3H, s), 1.51 (6H, d, J=0.7 Hz); LCMS (ESI) m/z 200.1 (M+H)+.

Provenance & Evidence