C([NH:9][C:10]([NH:12][C@@:13]([C:18]1[CH:23]=[C:22]([Br:24])[C:21]([F:25])=[CH:20][C:19]=1[F:26])([CH3:17])[CH2:14][CH2:15]O)=[S:11])(=O)C1C=CC=CC=1.Cl.[OH-].[Na+]>O1CCOCC1>[Br:24][C:22]1[C:21]([F:25])=[CH:20][C:19]([F:26])=[C:18]([C@:13]2([CH3:17])[CH2:14][CH2:15][S:11][C:10]([NH2:9])=[N:12]2)[CH:23]=1To a solution of (S)-1-benzoyl-3-[1-(5-bromo-2,4-difluoro-phenyl)-3-hydroxy-1-methyl-propyl]-thiourea (41 g, 68 mmoles) in 1,4-dioxane (20 mL) is added an aqueous solution of HCl (5 N, 407 mL, 2.0 moles, 30 equiv). The resulting suspension is warmed to 100° C. After stirring for 20 h, the reaction is concentrated under reduced pressure. The resulting mixture is treated with an aqueous solution of HCl (5 N, 407 mL, 2.0 moles) and stirred at 100° C. for 18 h. The suspension is cooled to 10° C. and the pH is adjusted to pH 10 with a 50% aqueous solution of NaOH. The resulting aqueous solution is extracted with ethyl acetate. The organic layers are combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel flash column chromatography eluting with a step gradient of hexane:acetone (4:1) to hexane:acetone (3:1) to give the title compound (57% yield, 85% purity as determined by LCMS): MS (m/z): 321, 323 (M+1).
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