反应详情

To a stirred solution of 2,4-dimethyl-thiazole-5-carboxylic acid (0.84 g, 5.34 mmol) in THF (50 mL) at −78° C. and under argon was added n-butyllithium (7.63 mL of a 1.40M solution in hexane, 10.7 mmol) dropwise. After 1 h, a solution of 5-methyl-3-phenyl-isoxazole-4-carbaldehyde (1.0 g, 5.34 mmol) in THF (50 mL) was added dropwise. After 3 h the reaction mixture was quenched with 10% aqueous citric acid (50 mL) then warmed to room temperature. The reaction mixture was extracted with ethyl acetate then the combined extracts were dried, filtered and concentrated. The resultant oil was redissolved in ethyl acetate, washed with water then dried, filtered and concentrated in vacuo. The resultant residue was dissolved in methanol (40 mL) and ether (20 mL) then (trimethylsilyl)diazomethane (4.0 mL of a 2M solution in ether, 8.0 mmol) was added dropwise. After 30 min, further (trimethylsilyl)diazomethane (4.0 mL of a 2M solution in ether, 8.0 mmol) was added. After 15 h, the reaction mixture was quenched with acetic acid (3 drops) then was concentrated and the residue redissolved in ethyl acetate and washed with NaOH (2 N). The organic phase was dried, filtered and concentrated then purified by chromatography (silica, 10 to 40% ethyl acetate in heptane) to give the title compound (500 mg, 26%) as a yellow foam. MS: m/e=359.0 [M]+.

1. customAfter 3 h the reaction mixture was quenched with 10% aqueous citric acid (50 mL)
2. extractionThe reaction mixture was extracted with ethyl acetate
3. customthe combined extracts were dried
4. filtrationfiltered
5. concentrationconcentrated
6. dissolutionThe resultant oil was redissolved in ethyl acetate
7. washwashed with water
8. customthen dried
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. dissolutionThe resultant residue was dissolved in methanol (40 mL)
12. additionether (20 mL) then (trimethylsilyl)diazomethane (4.0 mL of a 2M solution in ether, 8.0 mmol) was added dropwise
13. waitAfter 30 min
14. additionfurther (trimethylsilyl)diazomethane (4.0 mL of a 2M solution in ether, 8.0 mmol) was added
15. waitAfter 15 h
16. customthe reaction mixture was quenched with acetic acid (3 drops)
17. concentrationthen was concentrated
18. dissolutionthe residue redissolved in ethyl acetate
19. washwashed with NaOH (2 N)
20. customThe organic phase was dried
21. filtrationfiltered
22. concentrationconcentrated
23. customthen purified by chromatography (silica, 10 to 40% ethyl acetate in heptane)