Реакция #91538

Уравнение реакции

2-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)-5-(vinyloxy)pyridine

trimethyl(trifluoromethyl)silane

NaHCO3

sodium iodide

N2

→

title compound

Выход 82.0%

5-(2,2-difluorocyclopropoxy)-2-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridine

Выход 82.0%

Растворители

THF

brine

Условия реакции

Обработка

1. 1
   Экстракцияextracted with EtOAc (3×)
2. 2
   ДругоеThe combined organic layers were dried
3. 3
   Другоеwere removed under a gentle stream of N2
4. 4
   Другоеpurified by flash chromatography (SiO2, 5-25% EtOAc/Hexanes over 6 min, 25% for 4 min)

Методика

To a magnetically stirred mixture of 2-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)-5-(vinyloxy)pyridine (227 mg, 0.698 mmol) (prepared as in WO 2012/177635 A1) and trimethyl(trifluoromethyl)silane (1546 μL, 10.47 mmol) in dry THF (3034 μl) was added sodium iodide (84 mg, 0.558 mmol) in a 10 mL microwave vial under N2 atmosphere. The reaction mixture was stirred at 110° C. for 1 h 20 min Upon completion of the reaction in the microwave, the reaction was poured into a 1:1 mixture of brine and sat. aq. NaHCO3 and extracted with EtOAc (3×). The combined organic layers were dried by passing through a phase separator and volatiles were removed under a gentle stream of N2. The brown oil was loaded onto a pad of Celite® and purified by flash chromatography (SiO2, 5-25% EtOAc/Hexanes over 6 min, 25% for 4 min) to yield the title compound as a brown oil (215 mg, 82%): 1H NMR (400 MHz, CDCl3) δ 8.43 (d, J=2.8 Hz, 1H), 7.46 (d, J=8.7 Hz, 1H), 7.42-7.32 (m, 2H), 6.87-6.81 (m, 1H), 6.78-6.71 (m, 1H), 4.19-4.10 (m, 1H), 3.43 (t, J=4.8 Hz, 1H), 3.00-2.94 (m, 1H), 1.91 (dddd, J=14.4, 9.7, 8.8, 6.5 Hz, 1H), 1.71 (ddd, J=20.2, 9.8, 4.9 Hz, 1H); 19F NMR (376 MHz, CDCl3) δ −106.42-−107.22 (m, 1F), −107.77 (tdd, J=208.8, 70.6, 8.1 Hz, 2F), −109.34-−109.49 (m, 1F), −131.78 (dd, J=169.8, 1.2 Hz, 1F), −147.38 (dd, J=170.0, 4.6 Hz, 1F); ESIMS m/z 376 ([M+H]+).

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