C([Li])CCC.CC1(C)CCCC(C)(C)N1.[Br:16][C:17]1[CH:25]=[CH:24][C:20]([C:21]([OH:23])=[O:22])=[CH:19][N:18]=1.[I:26]I>O1CCCC1>[Br:16][C:17]1[CH:25]=[C:24]([I:26])[C:20]([C:21]([OH:23])=[O:22])=[CH:19][N:18]=1n-Butyllithium (2.5M in hexanes, 297 mL, 0.743 mol) was added over 1 h to a cooled (−25° C.) solution of 2,2,6,6,-tetramethylpiperidine (131 mL, 0.77 mol) in tetrahydrofuran (1 L). The mixture was left to stir for 16 h at −25° C. then cooled to −55° C. before addition of solid 6-bromonicotinic acid (50.0 g, 0.25 mmol). The mixture was allowed to warm to −20° C. and stirred for 2 h. The reaction mixture was cooled to −70° C. then poured onto a pre-cooled (−70° C.) solution of iodine (188.5 g, 0.74 mol) in tetrahydrofuran (500 mL). The mixture was then poured into the original reaction vessel and the contents allowed to warm to ambient temperature and stirred for 1 h. The solvent was evaporated and the resultant residue dissolved in water (500 mL) and washed with dichloromethane (3×300 mL). The aqueous phase was separated and the pH adjusted to 2 by the addition of concentrated hydrochloric acid. Aqueous sodium metabisulfite solution (20% w/w, 30 mL) was added and the solid which deposited was collected by filtration. The resultant solid was washed with water (75 mL) and pentane (75 mL) and dried at 75° C. under vacuum to furnish the title compound as a tan solid (53.1 g, 65%). 1H NMR (DMSO-D6, 300 MHz): 8.62 (s, 1H), 8.35 (s, 1H). LCMS (Method B): RT=2.16 min, M+H+=328/330.
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