Reaction #976713

Reaction equation

cesium carbonate

benzyl bromide

5-chloro-2-(trifluoromethyl)benzoic acid

DMA

→

title compound

Yield 57.0%

Benzyl 5-cyano-2-(trifluoromethyl)benzoate

Yield 57.0%

Conditions

Workup

1. 1
   ConcentrationConcentrate under reduced pressure
2. 2
   workup.ADDITIONadd water
3. 3
   Extractionextract with EtOAc
4. 4
   OtherSeparate the organic phase
5. 5
   Washwash with saturated aqueous NaCl
6. 6
   Dryingdry over MgSO4
7. 7
   Filtrationfilter
8. 8
   Concentrationconcentrate under reduced pressure

Procedure

Under a nitrogen atmosphere, to a solution of 5-chloro-2-(trifluoromethyl)benzoic acid (5.02 g, 22.35 mmol, 1.0 equiv) in DMA (45 mL), add zinc(II) cyanide (1.77 g, 15.07 mmol, 0.67 equiv), zinc dust (<10 μM, 330 mg, 5.05 mmol, 0.23 equiv), and bis(tri-tert-butylphosphino)palladium (540 mg, 1.06 mmol, 0.05 equiv). Stir the mixture under a nitrogen atmosphere at 95° C. for 9.5 hours. Add cesium carbonate (13.3 g, 40.82 mmol, 1.83 equiv), then benzyl bromide (3.0 mL, 25.15 mmol, 1.13 equiv), and stir under air at room temperature for 3.5 hours. Concentrate under reduced pressure, add water, and extract with EtOAc. Separate the organic phase and wash with saturated aqueous NaCl, dry over MgSO4, filter, and concentrate under reduced pressure. Subject the resulting crude material to flash chromatography on silica gel eluting with a 0-50% EtOAc/hexanes gradient to give the title compound (3.9 g, 57%). MS (m/z) 306 (M+1).

Source