CC([O-])(C)C.[K+].C([O:9][C:10](=[O:13])[CH2:11][SH:12])C.Cl[CH:15]=[C:16]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:17](=O)[CH3:18].CC[O-].[Na+]>C1COCC1.C(O)C>[CH2:20]([C:16]1[C:17]([CH3:18])=[C:11]([C:10]([OH:9])=[O:13])[S:12][CH:15]=1)[CH:21]([CH3:23])[CH3:22]
KOtBu (44.2 g, 394 mmol) is added portionwise to ethanol (200 mL). The mixture is stirred for 30 min at 20° C. to dissolve all KOtBu. Mercapto-acetic acid ethyl ester (47.3 g, 394 mmol) is added and the temperature is maintained at 20° C. This solution is slowly added at 20° C. to a solution of the crude 4-chloro-3-isobutyl-but-3-en-2-one (31.6 g, 197 mmol) in THF (350 mL). The mixture is stirred at rt for 15 h before sodium ethylate (13.4 g, 197 mmol) is added and stirring is continued at reflux for 1 h. The mixture is cooled to rt, and the solvents are evaporated on a rotavap. The residue is diluted with diethyl ether (500 mL), washed with 1 M aq. NaH2PO4 (200 mL), 1 N aq. NaOH (2×100 mL), sat. aq. NaHCO3 (35 mL) containing 10% aq. NaOCl (15 mL) and brine (100 mL), dried over Na2SO4, filtered and evaporated. The resulting residue (36.3 g) is dissolved in EtOH (250 mL), 2 N aq. LiOH (100 mL) is added, and the mixture is stirred at rt for 48 h before it is extracted with diethyl ether (1×400 mL, 2×150 mL). The organic extracts are washed with 1 N aq. NaOH (3×100 mL). The aq. extracts are carefully acidified with 25% aq. HCl and then extracted with DCM (3×150 mL). The combined DCM extracts are dried over MgSO4, filtered and evaporated. The crude product is purified by crystallisation from acetonitrile (150 mL) at 4° C. to give 4-isobutyl-3-methyl-thiophene-2-carboxylic acid (16.0 g) as a beige-brown crystalline powder; LC-MS: tR=0.95 min; 1H NMR (CD3OD): δ 7.21 (s, 1H), 2.43 (s, 3H), 2.42 (d, J=7.0 Hz, 2H), 1.83 (m, J=7.0 Hz, 1H), 0.92 (d, J=7.0 Hz, 6H).
Wird geladen…
