C([O:8][C@@H:9]([CH2:38][O:39]CC1C=CC=CC=1)[CH2:10][C:11]1([S:14]([NH:17][C:18]2[C:26]3[O:25][CH:24]=[CH:23][C:22]=3[C:21]([F:27])=[C:20]([F:28])[C:19]=2[NH:29][C:30]2[CH:35]=[CH:34][C:33]([I:36])=[CH:32][C:31]=2[F:37])(=[O:16])=[O:15])[CH2:13][CH2:12]1)C1C=CC=CC=1.B(Cl)(Cl)Cl.Cl.CCCCCCC>C(Cl)Cl.C(OCC(C)C)(=O)C>[F:27][C:21]1[C:22]2[CH:23]=[CH:24][O:25][C:26]=2[C:18]([NH:17][S:14]([C:11]2([CH2:10][C@@H:9]([OH:8])[CH2:38][OH:39])[CH2:12][CH2:13]2)(=[O:15])=[O:16])=[C:19]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([I:36])=[CH:32][C:31]=2[F:37])[C:20]=1[F:28]To a solution of (R)-1-(2,3-bis(benzyloxy)propyl)-N-(4,5-difluoro-6-((2-fluoro-4-iodophenyl)amino)benzofuran-7-yl)cyclopropane-1-sulfonamide (140 g, 183.6 mmol) in DCM (700 mL) was added 1M BCl3 solution in DCM (1.8 L, 1.84 mol) at −65-70° C. The mixture was stirred at −65˜−70° C. for 30 minutes until HPLC analysis showed the reaction had gone to completion. The cold solution was added to 1N HCl solution (1.8 L) at below 15° C., stirred for 15 mins and separated. The DCM layer was washed with water (2 L), the brine (1.5 L). DCM layer was concentrated to ˜250 mL and filtered to give white solid. The solid was dissolved in isobutyl acetate (240 mL) and heptane (500 mL) was added. The suspension was stirred overnight, filtered and dried to give 70 g of (R)—N-(4,5-difluoro-6-((2-fluoro-4-iodophenyl)amino)benzofuran-7-yl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide with 98.4% purity (65.5% yield, ee>99%).
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