反应详情

Sodium (10.7 g, 467 mmol) is dissolved in ethanol (500 mL) and the resulting solution is diluted with THF (100 mL) before mercapto-acetic acid ethyl ester (33.7 g, 280 mmol) dissolved in THF (70 mL) is slowly added at 5° C. The mixture is stirred at rt for 1 h before a solution of 3-chloro-2-isobutyl-but-2-enal (30 g, 187 mmol) in THF (100 mL) is slowly added at 8° C. The resulting yellow suspension is stirred at rt for 16 h. The reaction mixture is diluted with diethyl ether (500 mL) and is washed with dilute aq. NaOCl solution, followed by aq. 1N HCl and water. The organic extract is dried over MgSO4, filtered and evaporated. The remaining orange oil is dissolved in ethanol (150 mL) and 2N aq. LiOH (50 mL) is added. The mixture is stirred for 16 h at 50° C., acidified with 2 N aq. HCl and extracted with EA. The organic extract is dried over MgSO4, filtered and evaporated. The crude product is recrystallized from EA/heptane to give 4-isobutyl-5-methyl-thiophene-2-carboxylic acid (10.5 g) as colourless crystals; LC-MS: tR=0.92 min, [M+1+CH3CN]=240.16; 1H NMR (CDCl3): δ 7.59 (s, 1H), 2.40-2.37 (m, 5H), 1.84 (hept, J=7.0 Hz, 1H), 0.90 (d, J=7.0 Hz, 6H).

1. additionis slowly added at 5° C
2. additionis slowly added at 8° C
3. washis washed with dilute aq. NaOCl solution
4. extractionThe organic extract
5. dry with materialis dried over MgSO4
6. filtrationfiltered
7. customevaporated
8. dissolutionThe remaining orange oil is dissolved in ethanol (150 mL)
9. addition2N aq. LiOH (50 mL) is added
10. stirringThe mixture is stirred for 16 h at 50° C.
11. extractionextracted with EA
12. extractionThe organic extract
13. dry with materialis dried over MgSO4
14. filtrationfiltered
15. customevaporated
16. customThe crude product is recrystallized from EA/heptane