C([Li])CCC.CN(C)[CH2:8][CH2:9][N:10](C)[CH2:11][CH2:12]N(C)C.[F:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1.C(C1C=CN=CC=1)#N.C1C[O:37][CH2:36][CH2:35]1>>[F:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=1[C:36]([C:35]1[CH:8]=[CH:9][N:10]=[CH:11][CH:12]=1)=[O:37]Butyl lithium (70 ml of 2.22M solution, 155 mmole) was added to a solution of pentamethyldiethylenetriamine (23.3 ml, 155 mmole) in THF (250 ml) at -70° C. The solution was stirred for 5 min and 1,4-difluorobenzene (17.7 g, 155 mmole) in THF was added at -70° C. The solution was stirred for 2 hr during which time it was cooled to -75° C. and 4-cyanopyridine (15.6 g, 150 mmole) in THF was added at -75° C. The mixture was allowed to warm to 25° C. slowly and then quenched with ammonium chloride solution. The mixture was diluted with ether and the organic layer was separated. The organic layer was washed with water and 3N hydrochloric acid. The acid washes were stirred for 2 hr and basified with sodium hydroxide. The basic mixture was extracted with ether and the ether solution concentrated in vacuo. The crude product was purified by chromatography on silica eluting with ethyl acetate-hexane (20:1) to give 4-(2,5-difluorobenzoyl)pyridine (16.9 g, 51.5%).
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