Reacción #85698

Ecuación de reacción

NH4Cl

(R)—N—((S)-1-(4-(1-ethoxyvinyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide

chloroiodomethane

diethylzinc

→

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

Rendimiento 28.2%

Disolventes

toluene

MeOH CH2Cl2

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroReaction mixture
2. 2
   OtroReaction mixture
3. 3
   Temperaturawas cooled to 0° C. in an ice bath and to the cold reaction mixture
4. 4
   ExtracciónThe aqueous mixture was extracted with EtOAc
5. 5
   Lavadowashed with water, brine
6. 6
   Secadodried (Na2SO4)
7. 7
   Filtraciónfiltered
8. 8
   Concentraciónconcentrated onto silica gel

Procedimiento

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.

Fuente