Ethyl Thioglycolate → HCID 59497911, compound

Temperature

12.5 °C

Mercapto-acetic acid ethyl ester (9.86 g, 82.1 mmol) is slowly added to a solution of KOtBu (9.50 g, 84.7 mmol) in ethanol (50 mL) cooled to 10-15° C. The mixture is diluted with THF (100 mL) before a solution of the crude 1-chloro-2-isobutyl-4-methyl-pent-1-en-3-one (corresponds to 8.1 g, 43 mmol) in THF (50 mL) is added. The reaction mixture is stirred at 40° C. for 15 h, then at reflux for further 20 h, and at 35° C. for 48 h. The mixture is diluted with ether (300 mL) and washed with 1N aq. NaOH (3×100 mL), 1 M aq. KHSO4 (100 mL) and brine (100 mL). The organic phase is dried (Na2SO4), filtered and evaporated. The resulting residue is dissolved in ethanol (30 mL), 2 N aq. LiOH (30 mL) is added, and the mixture is stirred at reflux for 48 h. The mixture is extracted with diethyl ether, then the aq. phase is acidified with 25% aq. HCl and extracted with DCM. The organic extracts are dried (MgSO4), filtered and evaporated. The brown oil is diluted in acetonitrile (5 mL) and allowed to crystallize at 4° C. The crystalline material is collected, washed with acetonitrile and dried to afford pure 4-isobutyl-3-isopropyl-thiophene-2-carboxylic acid (98 mg) as pale yellow crystals; 1H NMR (CD3OD): δ 7.16 (s, 1H), 3.68 (hept, J=7.0 Hz, 1H), 2.48 (d, J=7.6 Hz, 2H), 1.84 (hept, J=7.0 Hz, 1H), 1.34 (d, J=7.0 Hz, 6H), 0.92 (d, J=6.4 Hz, 6H).

1. additionis added
2. temperatureat reflux for further 20 h
3. waitat 35° C. for 48 h
4. washwashed with 1N aq. NaOH (3×100 mL), 1 M aq. KHSO4 (100 mL) and brine (100 mL)
5. dry with materialThe organic phase is dried (Na2SO4)
6. filtrationfiltered
7. customevaporated
8. dissolutionThe resulting residue is dissolved in ethanol (30 mL)
9. addition2 N aq. LiOH (30 mL) is added
10. stirringthe mixture is stirred
11. temperatureat reflux for 48 h
12. extractionThe mixture is extracted with diethyl ether
13. extractionextracted with DCM
14. dry with materialThe organic extracts are dried (MgSO4)
15. filtrationfiltered
16. customevaporated
17. additionThe brown oil is diluted in acetonitrile (5 mL)
18. customto crystallize at 4° C
19. customThe crystalline material is collected
20. washwashed with acetonitrile
21. customdried

ORD record

ord-6245cd9315d04c9092337040acfbd429

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08003800B2