CC(C)COC(=O)[NH:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]2[CH2:18][CH2:17][S:16][CH2:15][CH2:14]2)=[C:9]([F:19])[CH:8]=1.[OH-].[K+]>C(O)CO.O.C(Cl)Cl>[F:19][C:9]1[CH:8]=[C:7]([NH2:6])[CH:12]=[CH:11][C:10]=1[CH:13]1[CH2:14][CH2:15][S:16][CH2:17][CH2:18]1A mixture of 2-methylpropyl[3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)phenyl]carbamate (Step 1, 2.12 g, 6.81 mmol) in ethylene glycol (25 mL) is treated with aqueous potassium hydroxide (45%, 25.5 g, 204 mmol) with vigorous stirring, and the mixture is heated to 95° C. and stirred at this temperature for 18 h. The reaction is then cooled to ambient temperature and diluted with water (50 mL) and CH2Cl2 (100 mL), the layers are separated, and the organic phase is washed with water (50 mL) and saline (20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product is chromatographed on a Flash 40M 90 g silica gel cartridge with a gradient of EtOAc/heptane (15/85–25/75), and those fractions with an Rf=0.32 by TLC (EtOAc/hexanes, 25/75) are pooled and concentrated to give the title compound, mp 96–98° C.; MS (ESI+) for C11H14NFS m/z 212 (M+H)+.
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