[F:1][C:2]1[CH:3]=[C:4]([C:9](=O)[CH2:10][CH2:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:5]=[C:6]([F:8])[CH:7]=1.[CH3:19][C:20]([S@@:23]([NH2:25])=[O:24])([CH3:22])[CH3:21].[BH4-].[Na+].CO>C1COCC1.[Cl-].[Na+].O.[O-]CC.[O-]CC.[O-]CC.[O-]CC.[Ti+4]>[C:20]([S@@:23]([NH:25][C@H:9]([C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=1)[CH2:10][CH2:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[O:24])([CH3:22])([CH3:21])[CH3:19]To a solution of ethyl 5-(3,5-difluorophenyl)-5-oxovalerate (5.00 g, 19.5 mmol) and (S)-2-methylpropane-2-sulfinamide (2.88 g, 23.8 mmol) in THF (123 mL) was added titanium tetraethoxide (8.18 mL, 39.0 mmol). The reaction vessel was quickly sealed and placed into a 60° C. bath for 16 h. After cooling to ambient temperature a septum and nitrogen inlet were attached prior to cooling to 0° C. Sodium borohydride (1.48 g, 39.0 mmol) was then added, and a complete reaction was observed after 1 h. Methyl alcohol was then slowly added until gas evolution had stopped. The reaction mixture was then diluted with brine (60 mL) while experiencing rapid stirring. The resultant slurry was filtered through celite, washing with EtOAc as needed. The combined organics were then washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to give an oil. This oil was purified by silica gel chromatography, eluting with a gradient of EtOAc:Hexanes—10:90 to 50:50, to give the title compound. MS: m/z=362 (M+1).
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