反应详情

To a stirred solution of 2,4-dimethylthiazole-5-carboxylic acid (1.26 g, 8.0 mmol) in THF (60 mL) at −78° C. and under argon was added BuLi (1.6M in hexanes, 10 mL, 16.0 mmol) dropwise. After 2 h at −75° C. a solution of 3-butyl-4-chloromethyl-5-methyl-isoxazole (1.5 g, 8.0 mmol) in THF (10 mL) was added dropwise. After 3.5 h the reaction mixture was quenched with citric acid solution (5%, 30 mL) then warmed to room temperature and extracted with ethyl acetate. The combined extracts were dried, filtered and concentrated to give the intermediate acid compound as a yellow oil. To a solution of intermediate acid in MeOH (30 mL) and diethylether (14 mL) was added trimethylsilyldiazomethane (2M in diethylether, 12 mL, 24 mmol) under ice cooling. Then the reaction mixture was quenched by addition of acetic acid (conc., 0.7 mL), evaporated and extracted with ethyl acetate. The combined extracts were washed with NaOH (2 N), water, dried over sodium sulfate, filtered and concentrated. Purification by chromatography (silica, 0 to 4% methanol in dichloromethane) afforded the title compound (1.51 g, 63%) as a yellow oil. MS: m/e=323.4 [M+H]+.

1. customAfter 3.5 h the reaction mixture was quenched with citric acid solution (5%, 30 mL)
2. extractionextracted with ethyl acetate
3. customThe combined extracts were dried
4. filtrationfiltered
5. concentrationconcentrated
6. customto give the intermediate acid compound as a yellow oil
7. customThen the reaction mixture was quenched by addition of acetic acid (conc., 0.7 mL)
8. customevaporated
9. extractionextracted with ethyl acetate
10. washThe combined extracts were washed with NaOH (2 N), water
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated
14. customPurification by chromatography (silica, 0 to 4% methanol in dichloromethane)