Реакция #85699

Уравнение реакции

CH2Cl2

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

4-isoxazoleboronic acid pinacol ester

potassium fluoride

→

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

Выход 52.0%

Растворители

DMSO

Условия реакции

Обработка

1. 1
   ДругоеThe reaction mixture was degassed with bubbling nitrogen (3 min)
2. 2
   Другоеthe vial capped
3. 3
   workup.ADDITIONThe reaction mixture was diluted with a saturated solution of NH4Cl
4. 4
   Экстракцияextracted with EtOAc
5. 5
   Промывкаwashed with water, brine
6. 6
   Сушкаdried (Na2SO4)
7. 7
   Фильтрацияfiltered
8. 8
   Концентрированиеconcentrated onto silica gel

Методика

To a microwave vial with a stir bar was added (R)—N—((S)-1-(4-bromo-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (300 mg, 0.93 mmol), 4-isoxazoleboronic acid pinacol ester (218 mg, 1.12 mmol), PdCl2(dppf).CH2Cl2 adduct (76 mg, 0.09 mmol), potassium fluoride (2.7 mL, 1.0 M in water, 2.79 mmol) and finally DMSO (9 mL). The reaction mixture was degassed with bubbling nitrogen (3 min) and the vial capped and heated in a preheated oil bath at 130° C. for 18 hours. The reaction mixture was diluted with a saturated solution of NH4Cl and extracted with EtOAc. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptanes 40 to 100%) provided (R)—N—((S)-1-(4-(cyanomethyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (136 mg, 0.48 mmol, 52% yield) as a viscous brown oil. 1H NMR (400 MHz, CDCl3) δ 1.19 (s, 9H) 1.57 (d, J=6.80 Hz, 3H) 3.39 (d, J=4.35 Hz, 1H) 3.74 (s, 2H) 4.81-4.88 (m, 1H) 7.04 (d, J=10.66 Hz, 1H) 7.11 (d, J=7.97 Hz, 1H) 7.38 (t, J=7.73 Hz, 1H). LCMS m/z 283.0 (M+H)+, Rt 0.72 min.

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