CC1(C)CCCC(C)(C)N1.[Li]CCCC.[F:16][C:17]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:18]=1[C:19]([OH:21])=[O:20].[I:28]I.Cl>C1COCC1>[F:16][C:17]1[C:25]([I:28])=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:18]=1[C:19]([OH:21])=[O:20]
To a solution of 2,2,6,6-tetramethylpiperidine (42 g, 298 mmol, 2.5 eq) in THF at −60° C. under N2 was added n-BuLi (2.2 M, 141 mL, 309.3 mmol, 2.6 eq) dropwise over a period of 30 min. The reaction mixture was stirred at −60° C. for 2 h, then a solution of 2-fluoro-5-methoxy-benzoic acid (15 g, 119 mmol, 1.0 eq) in THF (300 mL) was added dropwise with stirring. The reaction was stirred for a further 2 h at −60° C., then iodine (45 g, 179 mmol, 1.5 eq) was added in portions. The reaction was warmed to room temperature slowly and the resulting mixture acidified by addition of 1M HCl and extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:1) to give the title compound as a yellow solid (5.6 g, 16%).
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