Triethylamine → N,2-dimethoxy-N-methylacetamide

Temperature

0 °C

Triethylamine (115 mL) was added to a solution of methoxyacetic acid (35.0 g, 389 mmol) in CH2Cl2 (1200 mL) at room temperature. N,O-dimethylhydroxylamine hydrochloride (45.5 g, 467 mmol) was added, and after stirring for 5 min, the suspension was cooled to 0° C. Ethyl diazocarboxylate (EDC) (81.7 g, 428 mmol) was then added and the reaction mixture was stirred overnight while allowing it to warm to room temperature. The mixture was poured into a separatory funnel and diluted with CH2Cl2 (500 mL). The organic layer was washed with 1 N HCl (2×300 mL), saturated aqueous NaHCO3 solution (2×300 mL), and brine (300 mL). The resulting solution was dried over MgSO4, filtered and concentrated in vacuo. The product was purified by column chromatography on a short column of silica gel (5% methanol in CH2Cl2) to afford N,2-dimethoxy-N-methylacetamide (33.2 g, 64% yield) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 4.20 (s, 2H), 3.67 (s, 3H), 3.45 (s, 3H), 3.17 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 173.0, 69.7, 69.4, 61.4, 59.4; LRMS (ESI) m/e 134.1 [(M+H)+, calcd for C5H12NO3 134.1].

1. stirringthe reaction mixture was stirred overnight
2. temperatureto warm to room temperature
3. additionThe mixture was poured into a separatory funnel
4. washThe organic layer was washed with 1 N HCl (2×300 mL), saturated aqueous NaHCO3 solution (2×300 mL), and brine (300 mL)
5. dry with materialThe resulting solution was dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe product was purified by column chromatography on a short column of silica gel (5% methanol in CH2Cl2)

ORD record

ord-ea49fa06941949b9a7289dc572581368

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08436000B2