4-Methylmorpholine → Benzyl 2-{3-[methoxy(methyl)carbamoyl]cyclobutylidene}acetate

Participants

Reaction Steps

To an ice cold solution of 3-[2-(benzyloxy)-2-oxoethylidene]cyclobutane-1-carboxylic acid (2.0 g, 8.12 mmol), N-Methyl-morpholine (2.70 ml, 24.36 mmol) in DCM (50 ml) was added isobutyl chloroformate (1.70 ml, 12.99 mmol) drop-wise over 5 min. After an additional 5 min, methoxy(methyl)amine hydrochloride (1.58 g, 16.24 mmol) was added and the mixture was stirred overnight whilst allowing to warm to RT. The reaction mixture was then diluted with DCM (30 ml), washed with 0.1N HCl (50 ml) then sat. NaHCO3 (50 ml), dried over Na2SO4, filtered and evaporated. Purification by silica gel column chromatography, eluting with EtOAc:heptanes from 1:9 to 3:7 gave the desired product (1.54 g, 65%); MS (ESI+) for C16H19NO4 m/z 290.10 [M+H]+; HPLC purity 100% (ret. time, 1.86 min); 1H NMR (500 MHz, CHLOROFORM-d) δH ppm 2.96 (1 H, ddd, J=16.98, 8.79, 1.81 Hz), 3.17-3.30 (4 H, m), 3.30-3.48 (2 H, m), 3.51-3.63 (1 H, m), 3.64-3.75 (3 H, m), 5.15 (2 H, s), 5.73 (1 H, quirt, J=2.25 Hz), 7.29-7.42 (5 H, m).

Provenance & Evidence