Methanamine, N-methoxy-, hydrochloride (1:1) → 2-(1-Hexyn-1-yl)-N-methyl-N,4-bis(methyloxy)benzamide

Participants

Reaction Steps

A suspension of N,O-dimethylhydroxylamine hydrochloride (1.11 g, 11.2 mmol), in THF (35 mL) was cooled to −20° C. in a dry ice-acetonitrile bath. To this solution was added nBuLi (1.6 M in hexanes, 14.0 mL, 22.3 mmol). The mixture was stirred until all the salt had dissolved. A solution of methyl 2-(1-hexyn-1-yl)-4-(methyloxy)benzoate (78) (0.55 g, 2.23 mmol) in THF (2 mL) was added slowly. The mixture was allowed to warm up to room temperature and stirred at room temperature for 3 h, quenched with water and extracted with ether (3×50 mL). The combined ether extract was washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a brown oil. The crude product was purified by flash chromatography over SiO2 with hexanes:EtOAc (2.5:1) to yield 0.42 g (68%) of 79 as a light brown oil. 1H NMR (400 MHz, CDCl3): δ 0.92 (t, J=7.2 Hz, 3H), 1.40-1.55 (m, 2H), 1.55-1.65 (m, 2H), 2.39 (t, J=7.0 Hz, 2H), 3.28 (br s, 3H), 3.61 (br s, 3H), 3.80 (s, 3H), 6.83 (dd, J1=8.5 Hz, J2=2.5 Hz, 1H), 6.92 (d, J=2.5 Hz, 1H), 7.24 (d, J=8.6 Hz, 1H). LCMS (ESI): m/z 276 (M+H)+.

Provenance & Evidence