[F:1][CH:2]([F:5])[CH2:3][OH:4].[H-].[Na+].Cl[C:9]1[N:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:10]=1[C:11]([NH2:13])=[O:12]>COCCOC.CN(C)C=O.O>[Cl:18][C:16]1[CH:15]=[CH:14][C:10]([C:11]([NH2:13])=[O:12])=[C:9]([O:4][CH2:3][CH:2]([F:5])[F:1])[N:17]=12,2-Difluoroethanol (3.51 mL, 55.5 mmol) was added dropwise over 30 minutes to a suspension of NaH (2.22 g, 60% w/w dispersion in oil) in 1,2-dimethoxyethane (40.0 mL) at 14° C. and stirred for 1 hour. A portion of this solution (25 mL, 35 mmol) was added dropwise over 10 minutes to a solution of 2,6-dichloro-nicotinamide (5.30 g, 27.7 mmol) in dimethylformamide (40 mL) at 14° C. The resultant suspension was stirred for an additional 1 hour at 14° C., diluted with water (600 mL) and extracted with EtOAc (3×400 mL). The organic extracts were combined, dried over Na2SO4, filtered and concentrated to give title compound as a light orange solid (6.39 g, 97%). This was used without further purification.
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