反应详情

Sodium hydride (60% dispersion in oil, 1.37 g) in dry tetrahydrofuran (15 ml) was stirred at room temperature under an atmosphere of nitrogen and treated dropwise over 10 min. with a solution of 3-(5,6-dimethoxybenzo[b]thien-2-yl)-3-oxo-propanoic acid methyl ester (5.0 g) in dry tetrahydrofuran (75 ml). After 30 min. ethylbromoacetate (4.0 ml) was added and the reaction mixture was stirred at room temperature for a further 45 min. and then warmed to 40° C. After 2 hours the suspension was cooled, treated with glacial acetic acid (2 ml) then poured into water (400 ml). The mixture was extracted with diethyl ether (2×100 ml), the organic extracts were combined, washed with water (50 ml), dried (MgSO4), filtered and evaporated to dryness. The residue was dissolved in ethanol (25 ml), 5M hydrochloric acid (50 ml) was added and then the solution was heated at reflux for 10 hours. The resultant white suspension was cooled to room temperature and treated dropwise with 10M potassium hydroxide (30 ml). The reaction mixture was then stirred and heated at reflux under an atmosphere of nitrogen. After 1 hour the solution was cooled, diluted with water (100 ml) and extracted with ethyl acetate (50 ml). The aqueous layer was separated, stirred and acidified with 5M hydrochloric acid (10 ml). The resultant precipitate was filtered off, washed with water and dried at 65° C. under vacuum to give 4-(5,6-dimethoxy-benzo[b]thien-2-yl)-4-oxo-butanoic acid as a pale yellow solid (4.68 g). A portion crystallized from dichloromethane/methanol had m.p. 177°-178° C.

1. temperaturewarmed to 40° C
2. temperatureAfter 2 hours the suspension was cooled
3. extractionThe mixture was extracted with diethyl ether (2×100 ml)
4. washwashed with water (50 ml)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. customevaporated to dryness
8. dissolutionThe residue was dissolved in ethanol (25 ml)
9. addition5M hydrochloric acid (50 ml) was added
10. temperaturethe solution was heated
11. temperatureat reflux for 10 hours
12. temperatureThe resultant white suspension was cooled to room temperature
13. additiontreated dropwise with 10M potassium hydroxide (30 ml)
14. stirringThe reaction mixture was then stirred
15. temperatureheated
16. temperatureat reflux under an atmosphere of nitrogen
17. temperatureAfter 1 hour the solution was cooled
18. additiondiluted with water (100 ml)
19. extractionextracted with ethyl acetate (50 ml)
20. customThe aqueous layer was separated
21. stirringstirred
22. filtrationThe resultant precipitate was filtered off
23. washwashed with water
24. customdried at 65° C. under vacuum