C(NC(C)C)(C)C.C([Li])CCC.[Br:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[F:21].[C:22](=[O:24])=[O:23]>C1COCC1>[Br:13][C:14]1[C:15]([F:21])=[C:16]([CH:17]=[C:18]([Cl:20])[CH:19]=1)[C:22]([OH:24])=[O:23]To a cooled solution of diisopropylamine (2.4 mL, 17.2 mmol) in dry THF (15 mL) under Argon at 0° C. was added n-butyllithium (7.5 mL, 2.0 M in pentane, 15.0 mmol). After 30 minutes the solution was cooled to −78° C. and a solution of 2-bromo-4-chloro-1-fluorobenzene (3 g, 14.3 mmol) in dry THF (15 mL) was added over 15 minutes. After 1 hour, this solution was transferred via cannula over 10 minutes to a mixture of solid carbon dioxide and THF (30 mL) at −78° C. After 45 minutes the cold bath was removed and excess carbon dioxide was allowed to vent while the solution warmed to room temperature. The reaction mixture was then quenched with aqueous 0.5 M HCl solution (60 mL). After concentrating, the remaining aqueous phase was basified with aqueous 0.5 M NaOH solution and was washed with ethyl acetate (100 mL). The aqueous phase was then acidified with aqueous 1.0 M HCl solution and extracted with chloroform (2×75 mL). The combined organic portions were washed with brine, dried (Na2SO4) and concentrated to give 3.34 g of a semi-crystalline solid as a mixture of regioisomers with the desired isomer as the major: LCMS(m/z) not observed (MH+), tR=0.66 minute; 1H NMR (400 MHz, CDCl3) δ 7.80 (dd, J=5.5, 2.7 Hz, 1H), 7.95 (dd, J=5.5, 2.7 Hz, 1H).
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