Cyclopentanone → 3-Fluoro-4-(1-hydroxycyclopentyl)benzoic acid

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4-Bromo-3-fluoro-benzoic acid (3.00 g, 13.7 mmol) was dissolved in tetrahydrofuran (60 mL) and the solution was cooled to −78° C. n-Butyllithium (18.8 mL of 1.6 M in hexanes, 30 mmol) was added dropwise over 20 min while maintaining the internal temperature under −70° C. The reaction mixture was allowed to stir for 30 min at −78° C. and then cyclopentanone (1.21 mL, 13.7 mmol) was added in a dropwise while maintaining the internal temperature below −70° C. The mixture was stirred at −78° C. for 30 min the allowed to warm to room temperature. The reaction mixture was diluted with saturated NH4Cl (50 mL) and 1 M HCl (25 mL) and extracted with dichloromethane (3×50 mL). The combined extracts were dried over Na2SO4 and concentrated in vacuo. Silica gel chromatography (0-5% methanol/dichloromethane) provided 3-fluoro-4-(1-hydroxycyclopentyl)benzoic acid (400 mg, 13%) as a white solid. ESI-MS m/z calc. 224.1. Found 225.3 (M+1)+; Retention time: 1.16 minutes (3 min run). 1H NMR (400 MHz, DMSO-d6) δ 13.12 (s, 1H), 7.80-7.70 (m, 2H), 7.60-7.51 (m, 1H), 5.13 (s, 1H), 2.08-1.95 (m, 2H), 1.95-1.81 (m, 4H), 1.81-1.67 (m, 2H).

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