1-Bromo-2,4-difluorobenzene → (S)-N-((R)-2-(tert-butyldimethylsilyloxy)-1-(2,4-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide

Participants

Reaction Conditions

Reaction Steps

To a first flask was added magnesium turnings (197 mg, 8.11 mmol) and THF (7 mL). A 2.0 M solution of isopropyl magnesium chloride in THF (16 μL, 0.032 mmol) was added followed by 1-bromo-2,4-difluorobenzene (0.10 mL). The temperature of the reaction mixture raised to 30° C. Additional 1-bromo-2,4-difluorobenzene (0.91 mL) was added dropwise at such a rate that the internal temperature did not exceed 32° C. After addition, the reaction mixture was stirred at 26-28° C. for 30 minutes. To a second flask was added (S,E)-N-(2-(tert-butyldimethylsilyloxy)ethylidene)-2-methylpropane-2-sulfinamide (1.50 g, 5.41 mmol) and toluene (32 mL) under N2. The reaction mixture was cooled to −78° C. The Grignard reagent prepared in the first flask was slowly transferred to the reaction mixture in the second flask using a syringe. The reaction was allowed to slowly warm up to 0° C. The reaction was quenched by the addition of saturated aqueous NH4Cl solution. The organic layer was separated. The aqueous layer was extracted with EtOAc. The combined organic layer was washed with brine, dried and concentrated. The residue was purified by column chromatography (hexane/EtOAc, 6:1) to give (S)—N—((R)-2-(tert-butyldimethylsilyloxy)-1-(2,4-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (1.14 g, 54%) as a white solid.

Provenance & Evidence