Reaktion #91536

Reaktionsgleichung

6-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridin-3-ol

6-fluoronicotinonitrile

Cs2CO3

N2

→

title compound

Ausbeute 99.5%

6-((6-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridin-3-yl)oxy)nicotinonitrile

Ausbeute 99.5%

Lösungsmittel

DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction was quenched with water
2. 2
   Extraktionextracted with Et2O (3×)
3. 3
   SonstigeThe combined organic layers were dried
4. 4
   Sonstigewere removed under a gentle stream of N2
5. 5
   Sonstigepurified by flash chromatography (SiO2, 5-30% EtOAc/Hexanes over 8 min, 30% for 4 min)

Vorschrift

To a magnetically stirred mixture of 6-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridin-3-ol (500 mg, 1.671 mmol) and 6-fluoronicotinonitrile (224 mg, 1.838 mmol) in dry DMSO (5.570 mL) was added Cs2CO3 (653 mg, 2.005 mmol) in a 20 mL vial under N2 atmosphere. The reaction mixture was stirred at 25° C. for 16 h. The reaction was quenched with water and extracted with Et2O (3×). The combined organic layers were dried by passing through a phase separator and volatiles were removed under a gentle stream of N2. The resulting residue was loaded onto a pad of Celite® and purified by flash chromatography (SiO2, 5-30% EtOAc/Hexanes over 8 min, 30% for 4 min) to yield the title compound as a colorless oil (667 mg, 99%): 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J=2.2 Hz, 1H), 8.44 (dd, J=2.3, 0.7 Hz, 1H), 8.00 (dd, J=8.6, 2.3 Hz, 1H), 7.61 (dd, J=8.6, 2.5 Hz, 1H), 7.57 (dd, J=8.6, 0.7 Hz, 1H), 7.41 (dd, J=14.7, 8.2 Hz, 1H), 7.15 (dd, J=8.6, 0.7 Hz, 1H), 6.89-6.82 (m, 1H), 6.76 (ddd, J=9.8, 8.9, 2.5 Hz, 1H), 3.47 (d, J=4.9 Hz, 1H), 3.02-2.98 (m, 1H); 19F NMR (376 MHz, CDCl3) δ −106.85 (dd, J=258.0, 8.5 Hz, 1F), −107.45-−108.24 (m, 2F), −109.31 (q, J=8.5 Hz, 1F); ESIMS m/z 402 ([M+H]+).

Quelle