Sodium hydride → (S)-6-fluoro-3-(3-oxiranylmethoxy-phenyl)-benzo[d]isoxazole

Participants

Reaction Steps

To a cold (0° C.) solution of sodium hydride (1.83 g, 45.79 mmol) in dimethylformamide (120 mL) and under a nitrogen atmosphere, add a solution of 3-(6-fluoro-benzo[d]isoxazol-3-yl)-phenol (10 g, 43.63 mmol) in dimethylformamide (50 mL) and stir for 1 hour. Add, dropwise, (2S)-(+)-glycidyl tosylate (10.47 g, 45.87 mmol) dissolved in dimethylformamide (40 mL), over a period of time of 0.5 hours. Let reaction mixture warm to room temperature and stir for 2 days. Quench with water, concentrate and add ethyl acetate/water. Wash with water, saturated sodium chloride and dry (MgSO4) to give the crude compound. Purify by column (silica) chromatography eluting with a graded solvent mixtures of toluene to 1% ether in toluene to give the title compound as a white solid (10.07 g, 81% Yield). NMR and microanalysis (C, H, N) are consistent with the final, desired compound. Chiral HPLC, 18.14 minutes [Chiralcel OD (250×4.6 mm), 98:2 heptane/ethanol @ 0.8 mL/min, UV @ 285 nm, 18.14] shows the title compound as 88.3% e.e. mp=83-84° C.

Provenance & Evidence