CO.[H-].[Na+].[F:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=O)=[CH:8][CH:7]=1.C[O:15][C:16](=[O:24])[CH:17]([CH3:23])[CH2:18][C:19]([O:21][CH3:22])=[O:20]>C1(C)C=CC=CC=1>[CH3:22][O:21][C:19](=[O:20])[C:18](=[CH:10][C:9]1[CH:12]=[CH:13][C:6]([F:5])=[CH:7][CH:8]=1)[CH:17]([CH3:23])[C:16]([OH:24])=[O:15]After careful addition of absolute methanol (0.1 mL) to a suspension of sodium hydride (60% in mineral oil, 20 g, 0.5 mol) in anhydrous toluene (200 mL), a solution of 4-fluoro-benzaldehyde (31 g, 0.25 mol) and 2-methyl-succinic acid dimethyl ester (60 g, 0.38 mol) in anhydrous toluene (100 mL) was added at room temperature under a stream of nitrogen. The resulting mixture was stirred at room temperature for 30 minutes and then quenched by the slow addition of water (20 mL). The mixture was acidified by the addition of concentrated hydrochloric acid, and extracted with ethyl acetate (200 mL×3). The combined organic layers were dried over sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography (elution with 30% ethyl acetate in petroleum ether) to afford 2-(4-fluoro-benzylidene)-3-methyl-succinic acid 1-methyl ester (20 g, 33%) as a white solid. 1H NMR (400 MHz, acetone-d6) δ ppm 7.77 (s, 1H), 7.54 (d, J=8.8 Hz, 2H), 7.25 (d, J=8.8 Hz, 2H), 3.82 (q, 7.2 Hz, 1H), 1.40 (d, J=6.8 Hz, 3H).
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