Ethylacetate heptane → (R)-N-((S)-1-(4-bromo-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide

Temperature

0 °C

To a solution of (R,E)-N-(4-bromo-2-fluorobenzylidene)-2-methylpropane-2-sulfinamide (7.73 g, 25.2 mmol) in CH2Cl2 (252 mL), cooled to 0° C. (water/ice bath) under nitrogen, was added 3M methyl magnesium bromide (33.7 mL, 101 mmol) in Et2O. Reaction mixture allowed to stir for 30 min at 0° C., then gradually allowed to warm to room temperature and stirred for 1 hour at room temperature. Reaction mixture was cooled to 0° C. then quenched with the slow addition of a saturated solution of NH4Cl. Aqueous mixture extracted with EtOAc. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 40 to 100%) provided (R)—N—((S)-1-(4-bromo-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (4.93 g, 15.3 mmol, 60% yield) as a white crystalline solid. 1H NMR (400 MHz, CDCL3) δ 1.20 (s, 9H) 1.56 (d, J=6.70 Hz, 3H) 3.34 (br. s., 1H) 4.77-4.87 (m, 1H) 7.19-7.31 (m, 3H). LCMS m/z 324.0 (M+H)+, Rt 0.90 min.

1. customReaction mixture
2. temperatureto warm to room temperature
3. stirringstirred for 1 hour at room temperature
4. customReaction mixture
5. temperaturewas cooled to 0° C.
6. customthen quenched with the slow addition of a saturated solution of NH4Cl
7. extractionAqueous mixture extracted with EtOAc
8. washwashed with water, brine
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated onto silica gel

ORD record

ord-ca466d1cc97942b9a75abd15734fb2a5

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08957068B2