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

Temperature

-78 °C

(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).

1. custompurged
2. additionwas added via syringe
3. stirringThe reaction was stirred at −78° C. for five minutes
4. temperatureto warm to room temperature
5. customThe reaction was quenched with 1N HCl (˜5 mL)
6. additionwas diluted with H2O
7. extractionThe dilution was extracted three times with EtOAc
8. washwashed with brine solution
9. dry with materialdried over Na2SO4
10. filtrationfiltered through celite
11. concentrationconcentrated

ORD record

ord-ce12ffba6d684361b328cb81deb775ee

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06875765B2