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

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.

1. stirringThe solution was stirred overnight
2. washthe 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)
3. dry with materialdried over anhydrous magnesium sulfate
4. filtrationfiltered
5. customThe solvent was removed in vacuo

ORD record

ord-97d499a2ac064181a3469a172bf14636

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06359012B1