反应详情

Methyl 5-[(3-chlorophenyl)methyl]-4-{2-[(1,1-dimethylethyl)dimethylsilyl]oxyethoxy}thiophene-3-carboxylate (10.2 g) was dissolved in a mixture of 1M lithium hydroxide (50 ml), methanol (50 ml) and tetrahydrofuran (150 ml) and stirred for 18 hr. The reaction mixture was concentrated and the residue was partitioned between dichloromethane and 2M hydrochloric acid. The organic layer was collected, dried and filtered. t-Butyl-dimethylsilyl chloride (7 g) and imidazole (3.1 g) were added to the solution and the mixture was stirred for 72 hours. The reaction mixture was concentrated and the residue was dissolved in methanol. Potassium carbonate (5 g) was added to the solution and the suspension was vigorously stirred for 3 minutes, then filtered and concentrated. The residue was dissolved in ethyl acetate, washed with 2M hydrochloric acid, dried, filtered and concentrated. The residue was purified by chromatography, eluting with 10:1:1 isohexane:ethyl acetate:acetic acid, to give the sub-title compound (4.2 g).

1. concentrationThe reaction mixture was concentrated
2. customthe residue was partitioned between dichloromethane and 2M hydrochloric acid
3. customThe organic layer was collected
4. customdried
5. filtrationfiltered
6. additiont-Butyl-dimethylsilyl chloride (7 g) and imidazole (3.1 g) were added to the solution
7. stirringthe mixture was stirred for 72 hours
8. concentrationThe reaction mixture was concentrated
9. dissolutionthe residue was dissolved in methanol
10. additionPotassium carbonate (5 g) was added to the solution
11. stirringthe suspension was vigorously stirred for 3 minutes
12. filtrationfiltered
13. concentrationconcentrated
14. dissolutionThe residue was dissolved in ethyl acetate
15. washwashed with 2M hydrochloric acid
16. customdried
17. filtrationfiltered
18. concentrationconcentrated
19. customThe residue was purified by chromatography
20. washeluting with 10:1:1 isohexane