N-Methylpiperidine → N-Methoxy-N,2-dimethyl-1-naphthaleneacetamide

Participants

Reaction Conditions

Reaction Steps

(2-Methyl-naphthalen-1-yl)-acetic acid (3.55 g, 17.8 mmol) was stirred with N-methylpiperidine (2.48 mL, 21.4 mmol) in CH2Cl2 in an argon-purged, round-bottom flask. The mixture was chilled to −78° C. Isobutylchloroformate (2.53 mL, 19.5 mmol) was added via syringe. The reaction was stirred at −78° C. for twenty minutes and then a mixture of N,O-dimethylhydroxylamine hydrochloride (2.08 g, 21.3 mmol) and N-methylpiperidine (2.67 mL, 22.0 mmol) in CH2Cl2 (2 mL) was added via syringe. The reaction was stirred at −78° C. for five minutes and was then allowed to warm to room temperature. The reaction was quenched with 1N HCl (˜5 mL) and was diluted with H2O. The dilution was extracted three times with EtOAc. The organic extracts were combined, washed with brine solution, dried over Na2SO4, filtered through celite, and concentrated to give N-methoxy-N-methyl-2-(2-methyl-naphthalen-1-yl)-acetamide in quantitative yield. 1H NMR (300 MHz) CDCl3 δ 7.94 (d, J=8.8 Hz, 1H), 7.80 (d, J=8.7 Hz, 1H), 7.69 (d, J=8.4 Hz, 1H), 7.44 (m, 2H), 7.34 (d, J=8.2 Hz, 1H), 4.26 (s, 2H), 3.67 (s, 3H), 3.23 (s, 3H), 2.51 (s, 3H).

Provenance & Evidence