Reaktion #85698

Reaktionsgleichung

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

Ausbeute 28.2%

Lösungsmittel

toluene

MeOH CH2Cl2

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeReaction mixture
2. 2
   SonstigeReaction mixture
3. 3
   Temperaturwas cooled to 0° C. in an ice bath and to the cold reaction mixture
4. 4
   ExtraktionThe aqueous mixture was extracted with EtOAc
5. 5
   Waschenwashed with water, brine
6. 6
   Trocknendried (Na2SO4)
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated onto silica gel

Vorschrift

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.

Quelle