C(N(CC)CC)C.ClC(OCC(C)C)=O.[CH3:16][O:17][C:18](=[O:29])[C:19]1[CH:27]=[C:26]([F:28])[CH:25]=[C:21]([C:22](O)=[O:23])[CH:20]=1.[BH4-].[Na+]>ClCCl.O>[CH3:16][O:17][C:18](=[O:29])[C:19]1[CH:20]=[C:21]([CH2:22][OH:23])[CH:25]=[C:26]([F:28])[CH:27]=1
Triethylamine (2.2 ml, 16.0 mmol) and isobutyl chloroformate (1.0 ml, 8.0 mmol) were added to an ice-cooled solution of 5-fluoro-isophthalic acid monomethyl ester (1.3 g, 6.7 mmol) in dichloromethane (20 ml) and then warmed to room temperature. After stirring for 2 h, the reaction mixture was filtered and concentrated. The residue was re-dissolved tetrahydrofuran (10 ml) and then sodium borohydride (1.1 g, 29.02 mmol) in water (3 ml) was added drop-wise. After 1 h, the reaction was quenched with methanol and then diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated. Flash column chromatography on silica gel using 30% ethyl acetate in hexanes afforded 667 mg (54%) of 3-fluoro-5-hydroxymethyl-benzoic acid methyl ester as a colorless oil. 1H NMR (CDCl3), δ (ppm): 7.82 (s, 1H), 7.63 (d, 1H), 7.32 (d, 1H), 4.76 (s, 2H), 3.93 (s, 3H).
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