4-Methylmorpholine → HCID 59444289, compound

Participants

Reaction Steps

A dry 250 ml 3-neck flask, equipped with a reflux condenser and a thermometer, was charged with (R)-3-(methoxycarbonyl)-4-methylpentanoic acid (1.6 g, 9.19 mmol, which was prepared according to the procedure described in Robert J. Cregge et al., J. Med. Chem. 1998, 41, 2461-2480) and anhydrous acetonitrile (60 mL) under Argon. To the mixture was added N-methylmorpholine (2.020 mL, 18.37 mmol) followed by diphenylphosphoryl azide (1.979 mL, 9.19 mmol), and the mixture was stirred at rt for 1.5 hrs. After this time, 2-(trimethylsilyl)ethanol (6.58 mL, 45.9 mmol) was added to the mixture and the mixture was heated at 85° C. with stirring for 1 hr and 40 minutes. After cooling to rt, the solvent was evaporated off and the resulting residue was dissolved in EtOAc (˜100 ml). The resulting solution was washed with water, sat'd NaHCO3 (2×), 1N HCl and brine; dried over Na2SO4 and evaporated to give an oily residue. The oily residue was purified by Combiflash chromatography (220 g silica gel) eluting with 2:8 EtOAc-hexane to give 1.22 g of title compound. 1H NMR (CDCl3, 400 MHz) δ ppm 4.95 (1 H, br. s.), 4.03-4.22 (2 H, m), 3.70 (3 H, s), 3.40-3.54 (1 H, m), 3.23-3.34 (1 H, m), 2.38-2.53 (1 H, m), 1.97 (1 H, dq, J=13.62, 6.81 Hz), 1.26 (6 H, t, J=7.14 Hz), 0.97 (3 H, d, J=7.03 Hz), 0.94 (3 H, d, J=6.81 Hz), 0.00 (9 H, s).

Provenance & Evidence