Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1.C([Li])(C)(C)C.[C:14](#N)[C:15]1[C:16](=[CH:18][CH:19]=[CH:20][CH:21]=1)[NH2:17].Cl.C1C[O:27]CC1>C(OCC)(=O)C>[NH2:17][C:16]1[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=1[C:14]([C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1)=[O:27]A solution of 4-bromofluorobenzene (1 eq.) in THF was cooled to −78° C. under nitrogen and treated with tert-butyllithium (2.05 eq., 1.6 M solution in pentane) at a rate of 40 ml/h. The internal temperature did not rise above −74° C. The orange solution was stirred at −78° C. for 30 minutes prior to the addition of anthranilonitrile (0.6 eq.) as a solution in THF. The reaction was warmed to 0° C. and stirred for 2 hours. 3N HCl was added to the mixture and stirring continued for 30 minutes. The reaction was diluted with ethyl acetate and the layers were separated. The aqueous layer was back-extracted thrice with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified via HPLC eluting with 93:7 hexanes/ethyl acetate.
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