Benzyl Bromide → Benzyl 5-cyano-2-(trifluoromethyl)benzoate

Temperature

95 °C

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).

1. concentrationConcentrate under reduced pressure
2. additionadd water
3. extractionextract with EtOAc
4. customSeparate the organic phase
5. washwash with saturated aqueous NaCl
6. dry with materialdry over MgSO4
7. filtrationfilter
8. concentrationconcentrate under reduced pressure

ORD record

ord-060b2d212a454d7caae7414001d59693

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08252831B2