Chloroiodomethane → (R)-N-((S)-1-(4-(1-ethoxycyclopropyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide

To a round bottom flask containing (R)—N—((S)-1-(4-(1-ethoxyvinyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (0.49 g, 1.56 mmol) and chloroiodomethane (1.14 mL, 15.6 mmol) in toluene (15 mL) at 0° C. under argon was added diethylzinc (1.0M in hexanes) (15.6 mL, 15.6 mmol). Reaction mixture allowed to warm to room temperature and stirred for 1 hour. Reaction mixture was cooled to 0° C. in an ice bath and to the cold reaction mixture was slowly added a saturated solution of NH4Cl. The aqueous mixture was extracted with EtOAc. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (MeOH/CH2Cl2 0 to 10%) provided (R)—N—((S)-1-(4-(1-ethoxycyclopropyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (145 mg, 0.44 mmol, 28% yield) as a viscous brown oil. 1H NMR (300 MHz, CDCl3) δ 0.93-0.99 (m, 2H) 1.14-1.20 (m, 3H) 1.21 (s, 9H) 1.22-1.27 (m, 2H) 1.57-1.61 (m, 4H) 3.35 (d, J=4.98 Hz, 1H) 3.45 (q, J=7.07 Hz, 2H) 4.77-4.87 (m, 1H) 6.98 (dd, J=7.58, 1.43 Hz, 3H) 7.00-7.03 (m, 4H) 7.28-7.32 (m, 1H). LCMS m/z 328.1 (M+H)+, Rt 0.95 min.

1. customReaction mixture
2. customReaction mixture
3. temperaturewas cooled to 0° C. in an ice bath and to the cold reaction mixture
4. extractionThe aqueous mixture was extracted with EtOAc
5. washwashed with water, brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated onto silica gel

ORD-Eintrag

ord-1b2e35acfe004190b306a9856b743c71

Quelldatensatz

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09434719B2