Cl[C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([CH3:12])[N:5]=[CH:4][CH:3]=1.[Cl:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[C:16]([F:23])[CH:15]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])([O-])=O.[Cs+].[Cs+]>CC(N(C)C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([CH3:12])[N:5]=[CH:4][CH:3]=2)=[C:16]([F:23])[CH:15]=1A mixture of methyl 4-chloro-2-methylnicotinate (4 g, 21.55 mmol), (4-chloro-2-fluorophenyl)boronic acid (4.13 g, 23.71 mmol), tricyclohexylphosphine (1.813 g, 6.47 mmol), Pd(OAc)2 (0.484 g, 2.155 mmol) and Cs2CO3 (14.04 g, 43.1 mmol) in DMA (15 mL) was purged with nitrogen for 5 min and heated at 100° C. overnight (14 h). After cooling, the reaction mixture was filtered through diatomaceous earth (Celite®). DMA was removed under reduced pressure and the residue was diluted with ethyl acetate (10 mL). The organic phase was concentrated under reduced pressure and purified by silica gel column chromatography (EtOAc-hexane) to afford methyl 4-(4-chloro-2-fluorophenyl)-2-methylnicotinate (1 g, 3.58 mmol, 17% yield) as a red oil. LC/MS, (ESI) m/z 280.1 [(M+H)+, calcd for C14H12ClFNO2 280.0]; LC/MS retention time (method D): tR=0.80 min.
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