反应详情

温度

0 °C

To a stirred solution of (R)-3-((R)-2-hydroxymethyl-2-methyl-but-3-enoyl)-4-isopropyl-oxazolidin-2-one (724 mg, 3.00 mmol) and N,N,N′,N′-tetramethyl-1,8-naphthalenediamine (2.57 g, 11.0 mmol) in dichloromethane (15 mL) at 0° C. under nitrogen was added trimethyloxonium tetrafluoroborate (1.33 g, 9.00 mmol). The reaction was stirred at 0° C. for 15 minutes and then 4.5 h at ambient temperature. Saturated ammonium chloride solution was added and the mixture diluted with dichloromethane. The aqueous layer was separated and extracted with dichloromethane and the combined organic extracts washed with ammonium chloride solution, dried over anhydrous sodium sulfate filtered and evaporated. The residue was suspended in diethyl ether and filtered, the solids were washed with diethyl ether and the filtrate evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 1:0 to 4:1 followed by purification on an SCX cartridge eluting with methanol to give the title compound (263 mg, 34%) as a colourless oil. 1H NMR (300 MHz, CDCl3) δ 0.91 (app t, J=7.0 Hz, 6H), 1.50 (s, 3H), 2.32-2.43 (m, 1H), 3.35 (s, 3H), 3.46 (d, J=8.7 Hz, 1H), 4.19 (app dd, J=9.1, 3.6 Hz, 1H), 4.27 (app t, J=8.6 Hz, 1H), 4.50-4.57 (m, 1H), 5.00 (d, J=17.9 Hz, 1H), 5.12 (d, J=10.7 Hz, 1H), 6.19 (dd, J=17.9, 10.7 Hz, 1H). LCMS (m/z) 256.2 [M+H], Tr=2.53 min.

1. custom4.5 h
2. customat ambient temperature
3. customThe aqueous layer was separated
4. extractionextracted with dichloromethane
5. washthe combined organic extracts washed with ammonium chloride solution
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. customevaporated
9. filtrationfiltered
10. washthe solids were washed with diethyl ether
11. customthe filtrate evaporated
12. customThe residue was purified by silica gel chromatography
13. customfollowed by purification on an SCX cartridge
14. washeluting with methanol