Hydrochloric Acid → HCID 86732167, compound

Temperature

-78 °C

To a 250 mL round-bottomed flask was added (R)-N-((S)-2-(6-bromo-3-fluoropyridin-2-yl)-1-fluoro-4-oxobutan-2-yl)-2-methylpropane-2-sulfinamide (5.9 g, 15.39 mmol) and THF (130 mL). The mixture was cooled to −78° C. and (trifluoromethyl)trimethylsilane (Apollo Scientific Ltd.; 24.46 mL, 154 mmol) was added. After stirring for 10 min, tetrabutylammonium fluoride (Aldrich; 27.7 mL, 27.7 mmol, 1.0 M in THF) was added over 10 min. The solution was stirred at −78° C. for 2 h. To the solution was added 1 N HCl (10 mL) and the solution was allowed to warm to rt. The solution was carefully diluted with water (50 mL) and extracted with EtOAc (2×100 mL). The combined extracts were washed with water (100 mL) and brine (50 mL) and then dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (Gradient: 0.0 to 60% EtOAc/hexane, 120 g Silicycle HP) afforded:

1. stirringThe solution was stirred at −78° C. for 2 h
2. temperatureto warm to rt
3. extractionextracted with EtOAc (2×100 mL)
4. washThe combined extracts were washed with water (100 mL) and brine (50 mL)
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated onto silica
7. customPurification by silica gel chromatography (Gradient: 0.0 to 60% EtOAc/hexane, 120 g Silicycle HP)
8. customafforded

ORD record

ord-959d914dcd584717932a60f15ff7718a

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296734B2