N,O-Dimethylhydroxylamine Hydrochloride

• N,O-Dimethylhydroxylamine Hydrochloride [D1899]
• Acryloyl Chloride
• Sodium Hydrogen Carbonate [S0561]
• Dichloromethane

N,O-Dimethylhydroxylamine hydrochloride (646.7 mg, 6.63 mmol, 1.2 eq.) was added to a solution of acryloyl chloride (0.45 mL, 500 mg, 5.52 mmol) and NaHCO₃ (1.16 g, 13.8 mmol, 2.5 eq.) in dry dichloromethane (4.6 mL) at 0 °C. The mixture was stirred for overnight at room temperature. The reaction mixture was quenched with 3 mol/L HCl (10 mL) and the two layers were separated. The organic layer was washed with sat. NaHCO₃ aq. (10 mL) and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give the Weinreb amide 1 as a colorless liquid (413 mg, 65% yield).

The reaction mixture was monitored by TLC (ethyl acetate:hexane = 1:1, Rf = 0.55).

Weinreb amide 1

¹H NMR (270 MHz, CDCl₃); δ 6.74 (dd, J = 10.1, 17.1 Hz, 1H), 6.43 (dd, J = 2.3, 17.1 Hz, 1H), 5.76 (dd, J = 2.3, 10.1 Hz, 1H), 3.71 (s, 3H), 3.27 (s, 3H).

• Concise stereoselective and stereodivergent syntheses of (±)-melicolones A and B
• Z. Wang, S. F. Martin, Tetrahedron 2022, 103, 132551.