反应详情

A cooled (0° C.) solution of (S)-3-{2-[1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-methyl-but-3-enoyl}-4-isopropyl-oxazolidin-2-one (1.729 g, 4.677 mmol) in tetrahydrofuran/water (60 mL, 2:1) was subsequently treated with hydrogen peroxide (30% aqueous, 2.4 mL, 23.385 mmol) and lithium hydroxide monohydrate (392.4 mg, 9.355 mmol). After stirring for 2 days at room temperature, hydrogen peroxide (30% aqueous, 2.4 mL, 23.385 mmol) and lithium hydroxide monohydrate (400 mg, 9.535 mmol) were added at 0° C. After stirring at room temperature for 4 days, the reaction was quenched with solid sodium metabisulfite (18 g). After stirring for 1 h at room temperature, the pH was adjusted with hydrochloric acid (1 M) to pH 2 at 0° C. The aqueous layer was extracted with ethyl acetate (2×). The organics were combined, dried over anhydrous sodium sulfate, filtered and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 100 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/diethyl ether 1:0 to 7:3 to afford the title compound (488.0 mg, 40%) as a yellow solid and as a single pair of enantiomers along with unreacted (S)-3-{2-[1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-methyl-but-3-enoyl}-4-isopropyl-oxazolidin-2-one (431.5 mg, 25%, LCMS (m/z) 370.1 [M+H], Tr=3.93 min) as the other single pair of enantiomers as a colourless oil. 1H NMR (300 MHz, CDCl3) δ 0.12 (s, 6H), 0.92 (s, 9H), 1.18 (d, J=6.0 Hz, 3H), 1.34 (s, 3H), 3.99 (q, J=6.2 Hz, 1H), 5.18 (d, J=17.8 Hz, 1H), 5.28 (d, J=10.5 Hz, 1H), 6.22 (dd, J=17.6, 11.2 Hz, 1H).

1. stirringAfter stirring at room temperature for 4 days
2. customthe reaction was quenched with solid sodium metabisulfite (18 g)
3. stirringAfter stirring for 1 h at room temperature
4. customwas adjusted with hydrochloric acid (1 M) to pH 2 at 0° C
5. extractionThe aqueous layer was extracted with ethyl acetate (2×)
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. customthe volatiles were removed in vacuo
9. customThe residue was purified by silica gel chromatography
10. washeluted with a continuous gradient of iso-hexanes/diethyl ether 1:0 to 7:3