[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:14][CH3:15])[C:9]=1[O:10][CH:11]([CH3:13])[CH3:12])[CH:5]=[O:6].CC(=CC)C.Cl([O-])=[O:22].O.P([O-])(O)(O)=O.[Na+].[OH-].[Na+]>O.C(O)(C)(C)C>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:14][CH3:15])[C:9]=1[O:10][CH:11]([CH3:12])[CH3:13])[C:5]([OH:22])=[O:6]A solution of 3-fluoro-4-hydroxy-5-methoxy-benzaldehyde (250 mg, 1.5 mmol) in DMF (2.5 mL) was treated with potassium carbonate (812 mg, 5.9 mmol) and stirred for 30 minutes. 2-Iodopropane (500 mg, 2.9 mmol) was added over 10 minutes and reaction mixture was stirred for 20 hours. The reaction mixture was partitioned between EtOAc and saturated aqueous sodium chloride solution. The organic layer was washed with saturated sodium bicarbonate solution. The organic layer was separated and dried over sodium sulfate, filtered and concentrated in vacuo to give 3-fluoro-4-isopropoxy-5-methoxybenzaldehyde. To the aldehyde was added tert-butanol (6.7 mL) and 2-methylbut-2-ene (4 mL, 38.2 mmol) and the reaction mixture was cooled to 0° C. A solution of chlorite (345 mg, 3.8 mmol) and sodium dihydrogen phosphate hydrate (527 mg, 3.8 mmol) in water (6.7 mL) was added dropwise over 5 minutes, and the reaction mixture was stirred 30 minutes. The reaction mixture was warmed to room temperature and stirred for 12 hours. The reaction mixture was basified with 1 N NaOH solution and extracted with ethyl acetate (2×50 mL). The aqueous layer was acidified with 1 N HCl solution and extracted with EtOAc (4×50 mL). The combined organics were dried (Na2SO4), filtered, and concentrated in vacuo to afford 3-fluoro-4-isopropoxy-5-methoxy-benzoic acid (190 mg, 56%) as a white solid. ESI-MS m/z calc. 228.0. Found 229.3 (M−1)+; Retention time: 1.57 minutes (3 min run).
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