N,O-Dimethylhydroxylamine → tert-Butyl 3-(methoxy(methyl)carbamoyl)azetidine-1-carboxylate

Participants

Reaction Steps

To a solution of azetidine-1,3-dicarboxylic acid mono-tert-butyl ester (Alfa, 5.0 g, 24.9 mmol) in THF (80 mL) was added DIEA (9.55 mL, 54.7 mmol) and HATU (11.34 g, 29.8 mol) and the reaction mixture was stirred at ambient temperature for 1.5 h. N,O-dimethylhydroxylamine (1.82 g, 29.8 mmol) was added and the reaction mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with aqueous NH4Cl (100 mL). The aqueous layer was extracted with EtOAc (3×100 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL), dried over Na2SO4, filtered and evaporated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 15% EtOAc in petroleum ether) to give 3-(methoxy-methyl-carbamoyl)-azetidine-1-carboxylic acid tert-butyl ester (6.0 g, 99.0%). 1H NMR (DMSO-d6, 400 MHz): δ 4.02 (m, 4H), 3.71 (m, 1H), 3.63 (s, 3H), 3.11 (s, 3H), 1.38 (s, 9H).

Provenance & Evidence