Methanol → Methyl (δS)-δ-[[(S)-(1,1-dimethylethyl)sulfinyl]amino]-3,5-difluoro-α,α-dimethylbenzenepentanoate

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Reaction Steps

To a solution of methyl 5-(3,5-difluorophenyl)-2,2-dimethyl-5-oxopentanoate from Step D (500. mg, 1.85 mmol) and (S)-2-methylpropane-2-sulfinamide (336 mg, 2.78 mmol) in THF (6.5 mL), was added titanium tetraethoxide (616 mg, 2.52 mmol). The reaction vessel was quickly sealed and placed into a 60° C. bath for 3 hours. After cooling to ambient temperature a septum and nitrogen inlet were attached prior to cooling to 0° C. Sodium borohydride (191 mg, 5.05 mmol) was then added, and a complete reaction was observed after 15 minutes. Methyl alcohol was then slowly added until gas evolution had stopped. The reaction mixture was then diluted with saturated brine (6.5 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 70:30, to give the title compound containing about 12% of the corresponding ethyl ester. MS: m/z=376 (M+1).

Provenance & Evidence