C([O-])(=O)C.[Na+].[Br:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1I.[C:23]([O:27][CH2:28][CH3:29])(=[O:26])[CH:24]=[CH2:25].O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN1C(=O)CCC1>[CH2:28]([O:27][C:23](=[O:26])[CH:24]=[CH:25][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[CH2:15][O:14][C:8]1[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:7]=1[Br:6])[CH3:29]To a clean, dry 100-gallon reactor with stirring under nitrogen add fresh N-methylpyrrolidinone (72 L), sodium acetate (2721 g, 33.17 mol), 1-bromo-4-fluoro-2-(2-iodo-benzyloxy)-benzene (9000 g, 22.11 mol) and tetrabutylammonium bromide (7128 g, 22.11 mol). Initiate stirring and de-gas the reaction mixture under full vacuum for 30 min, purging with nitrogen. Allow the reactor to return to ambient pressure under nitrogen and repeat the degassing procedure. Add palladium (II) acetate (180 g, 2%/weight) to the reaction mixture and heat to 60° C. At 60° C., slowly add ethyl acrylate (2258 g, 22.55 mol) as a solution in N-methyl pyrrolidinone (18 L) to the reaction mixture via the addition funnel. Upon completion of the addition, heat the reaction mixture to 70° C. Continue to stir for a minimum of 2 h at 70° C. Adjust the internal temperature of the reaction mixture to 5-10° C. To a separate, clean, appropriately sized reactor, charge water (225 L), initiate vigorous stirring and cool to an internal temperature of ≦5° C. Transfer the reaction mixture to the vigorously stirring water over a minimum of one hour. Stir the resulting suspension for 30 min to one hour at ambient temperature. Filter through a polypropylene filter pad to collect the light purple solids. Wash the filter cake with water (25 L) and pull dry on the filter using a rubber dam. Recharge the solids to the reactor with water (45 L) and stir the suspension for 30 min to one hour. Re-filter the solids onto a polypropylene filter pad, washing the filter cake with water (25 L). Pull dry on the filter using a rubber dam. Transfer the light purple material to drying trays and air dry in a fume hood for a minimum of 24 h. Oven dry the solids under vacuum at <50° C. to obtain the title compound (8.4 kg, 100%).
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