Cesium carbonate → N-(2,4-dimethylphenyl)-3,5-difluoro-N-isobutyl-4-vinylbenzenesulfonamide

Temperature

140 °C

To a vial was added potassium trifluoro(vinyl)borate (0.744 g, 5.55 mmol), triphenylphosphine (0.073 g, 0.278 mmol), 4-bromo-N-(2,4-dimethylphenyl)-3,5-difluoro-N-isobutylbenzenesulfonamide (2 g, 4.63 mmol) suspension in tetrahydrofuran (THF) (22 mL), cesium carbonate (4.52 g, 13.88 mmol), water (2.200 mL) and palladium(II) chloride (0.016 g, 0.093 mmol). The mixture was divided evenly between two microwave vials and the vessels then sealed and heated by microwaves (Biotage Initiator) to 140° C. for 30 minutes. LCMS analysis showed some conversion, so additional 0.5 equivalent of potassium trifluoro(vinyl)borate was added to each reaction, along with extra water (2 mL) and THF (2 mL). The reactions were reheated by microwaves for a further 1 hour at 140° C. The reactions were then diluted with dichloromethane (5 mL) and water (2 mL), filtered through celite and dried using a hydrophobic frit. The organics were concentrated and purified by flash silica (Si) chromatography (0-25% ethyl acetate-cyclohexane gradient). The appropriate fractions were combined and evaporated in vacuo to give two batches of the required product, 769 mg and 856 mg, as yellow oils. LCMS [LCMS2] Rt 1.60 min, m/z (ES+) 380 (M+H).

1. customthe vessels then sealed
2. filtrationfiltered through celite
3. customdried
4. concentrationThe organics were concentrated
5. custompurified by flash silica (Si) chromatography (0-25% ethyl acetate-cyclohexane gradient)
6. customevaporated in vacuo

ORD record

ord-18a993b94ba04b60ba6fb44a910eab14

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428452B2