Imidazole → (2S)-(+)-N-methoxy-N-methyl-2,3-dimethyl-2-hydroxybutyramide

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Reaction Steps

To a magnetically stirred solution of (8) (59 g, 0.44 mol) in methylene chloride (880 mL) in a 3-L, two-neck, round-bottom flask at 0° C. under a nitrogen atmosphere was added 1,1-carbonyldiimidazole (87 g, 0.54 mol, 1.2 equivalents) in portions. The yellow solution was gradually warmed to room temperature and stirred under a nitrogen atmosphere overnight. To the reaction was added imidazole (60 g, 0.88 mol, 2 equivalents), 4-dimethylaminopyridine (1.6 g, 0.01 mol, 0.03 equivalents), and N,O-dimethylhydroxylamine hydrochloride (53 g, 0.54 mol, 1.2 equivalents). The solution was stirred overnight and then the resulting mixture was washed with 2N aqueous hydrochloric acid (2×600 mL), water (1×800 mL), and saturated aqueous sodium chloride solution (1×800 mL), dried over anhydrous magnesium sulfate, and filtered. The solvent was removed in vacuo to provide 73 g (94% yield) of (9) as a yellow oil. The 1H NMR spectrum of the product was consistent with the material previously prepared.

Provenance & Evidence