Reaction #2487440

Reaction equation

3-chloro-2-((6-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridin-3-yl)oxy)-5-(trifluoromethyl)pyridine

1H-tetrazole

potassium carbonate

→

title compound

1-(5-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol

Solvents

DMSO

DCM

—

ice

Conditions

Workup

1. 1
   Temperaturecooled to RT
2. 2
   Otherthe layers were separated on a Phase Separator
3. 3
   ExtractionThe aq. layer was extracted again with DCM
4. 4
   Otherthe combined organic extracts were evaporated
5. 5
   OtherThe crude residue was purified on silica (ISCO, 40 gram column, gradient to 40% EtOAc/Hexanes over 20 minutes)

Procedure

To a magnetically stirred mixture of 3-chloro-2-((6-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridin-3-yl)oxy)-5-(trifluoromethyl)pyridine (U) (356 mg, 0.744 mmol) and 1H-tetrazole (62.5 mg, 0.892 mmol) in dry DMSO (3.718 mL) was added potassium carbonate (206 mg, 1.487 mmol) in a dry 25 mL vial under N2 atmosphere. The reaction mixture was stirred at 60° C. overnight, cooled to RT and diluted with ice-cold water/2N HCl and DCM and the layers were separated on a Phase Separator. The aq. layer was extracted again with DCM and the combined organic extracts were evaporated. The crude residue was purified on silica (ISCO, 40 gram column, gradient to 40% EtOAc/Hexanes over 20 minutes) to afford the title compound. Yield=119 mg (27.7%) of a brown glass. 1H NMR (400 MHz, CDCl3) δ 8.76 (s, 1H), 8.50 (d, J=2.3 Hz, 1H), 8.27 (dd, J=2.1, 0.9 Hz, 1H), 8.05 (d, J=2.0 Hz, 1H), 7.74-7.63 (m, 2H), 7.34 (td, J=8.9, 6.4 Hz, 1H), 7.21 (s, 1H), 6.83-6.72 (m, 1H), 6.72-6.64 (m, 1H), 5.64 (d, J=14.3 Hz, 1H), 5.13 (d, J=14.1 Hz, 1H). 1H-decoupled 19F NMR (376 MHz, CDCl3) δ −61.74 (s), −103.20 (d, J=15.0 Hz), −103.72-−104.09 (m), −107.86 (d, J=10.9 Hz), −110.78 (d, J=45.0 Hz), −111.48 (d, J=45.0 Hz). MS(ESI): m/z 549.1 (M+H)+.

Source