Hydrogen Peroxide → HCID 86650530, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 37 g (70 mmol) of (4S)-4-benzyl-3-{(2R)-2-[(S)-{[tert-butyl(dimethyl)silyl]oxy}(6-chloropyridin-3-yl)methyl]hex-5-ynoyl}-1,3-oxazinan-2-one from Step C above in 520 mL of a 3 to 1 mixture of anhydrous tetrahydrofuran to water at 0° C. under an atmosphere of nitrogen was added 30 mL (350 mmol) of a 35% aqueous hydrogen peroxide solution at a rate slow enough to keep the internal temperature below 3° C. Next, 140 mL (140 mmol) of a 1.0 M aqueous sodium hydroxide solution was added at a rate slow enough to keep the internal temperature of the reaction below 5° C. After complete addition the resulting mixture was stirred for 18 h at 0° C. then quenched with a solution of 350 mL (420 mmol) of a 1.2 M aqueous sodium sulfite solution at a rate slow enough to keep the internal temperature of the mixture below 15° C. All volatiles were removed in vacuo and the remaining aqueous phase was cooled to 0° C. and acidified with a 2.5 M aqueous hydrogen chloride solution until a pH of 3 was achieved. The aqueous phase was then extracted with ethyl acetate (3×200 mL) and the combined organics were washed with brine (10 ml), dried over magnesium sulfate, filtered and evaporated in vacuo. The residue was purified by silica gel chromatography eluting with 15% ethyl acetate and 3% acetic acid in hexanes to afford the title compound as a white solid (16 g, 62%). LC-MS: m/z (ES) 368.2 (MH)+.

Provenance & Evidence