Imidazole → 2-((3S)-4-{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxybutyl)-6-methoxyphenol

Participants

Reaction Steps

To a solution of (2S)-4-[2-(benzyloxy)-3-methoxyphenyl]-1,2-butanediol (8.00 g, 26.5 mmol) in N,N-dimethylformamide (250 mL) cooled to 0° C. was added tert-butyldimethylsilyl chloride (4.39 g, 29.1 mmol) followed by imidazole (2.16 g, 31.8 mmol) and the reaction mixture was allowed to stir at room temperature for 4 h. The reaction mixture was diluted with water (500 mL) and ethyl acetate (200 mL). The aqueous phase was separated and extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with aqueous hydrogen chloride (200 mL), water (4×200 mL), aqueous sodium chloride (300 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude oil. The residue was dissolved in ethanol (300 mL), palladium on carbon (10 wt. %, 1.00 g) was added, and the reaction mixture was shaken under an H2 atmosphere (50 psi) for 6 h. The reaction mixture was filtered (celite) and the solvent removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, ethyl acetate:hexanes 1:4) gave 7.33 g (85%, 40% ee) of 2-((3S)-4-{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxybutyl)-6-methoxyphenol as a colorless oil which crystallized upon standing. Rf=0.53 (silica, ethyl acetate:hexanes 1:4); mp 44-46° C.; Anal. Calcd. for C17H30O4Si: C, 62.54; H, 9.26. Found: C, 62.41; H, 9.19.

Provenance & Evidence