[Cl:1][C:2]1[S:6][C:5]([S:7]([NH:10][C@H:11]([CH:19]=[O:20])[C@H:12]([CH3:18])[CH2:13][C:14]([F:17])([F:16])[F:15])(=[O:9])=[O:8])=[CH:4][CH:3]=1.[CH3:21][Mg]Br.CCOC(C)=O.CCCCCC>C1COCC1>[Cl:1][C:2]1[S:6][C:5]([S:7]([NH:10][C@H:11]([CH:19]([OH:20])[CH3:21])[C@H:12]([CH3:18])[CH2:13][C:14]([F:15])([F:16])[F:17])(=[O:9])=[O:8])=[CH:4][CH:3]=1A solution of 5-chloro-N-[(1S,2R)-4,4,4-trifluoro-1-formyl-2-methylbutyl]thiophene-2-sulfonamide (prepared as in Example 16, 1.0 g, 2.86 mmol) in THF (10 mL) was stirred under nitrogen at 0° C. Methyl magnesium bromide (3.0 M in ethyl ether, 1.9 mL, 5.71 mmol.) was added dropwise and the resulting solution was stirred for 1 h at 25° C. After this time period, the reaction was complete by TLC (1:2 EtOAc/hexane). The solution was quenched with saturated aqueous NH4Cl (10 mL) and extracted with ether (40 mL). The organic layer was washed with brine (20 mL) and then dried over MgSO4 to obtain a crude oil (0.867 g). The crude product was purified by the Biotage Flash™ 60 chromatography system, eluent: 1:6 EtOAc-hexanes, to afford 5-chloro-N-[(1S,2R)-4,4,4-trifluoro-1-(1-hydroxyethyl)-2-methyl butyl]thiophene-2-sulfonamide as a colorless oil (0.495 g, 49.5%). Mass Spectrum (−ESI): 364 (M−H)−.
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