tert-Butanol → 2,2-Bis(3-(trifluoromethoxy)phenyl)acetonitrile

To a solution of bis(3-(trifluoromethoxy)phenyl)methanone (9.94 g, 28.4 mmol), prepared as described in Procedure 13, in DME (200 mL) was added TosMIC (7.49 g, 38.3 mmol). The reaction mixture was cooled in an ice-bath and a 1.0 M solution of t-BuOK in t-BuOH (77 mL, 77 mmol) in DME (77 mL) was added via cannula as a slow stream. Upon completion of addition, the ice-bath was removed and the reaction mixture was stirred at rt for 16 h. After this time, additional TosMIC (3.75 g, 19.2 mmol) was added at rt and the reaction mixture was stirred for an additional hour. At the conclusion of this period, the reaction was poured into H2O (150 mL) and extracted with hexane (3×200 mL). The organic portions were combined and dried over Na2SO4, filtered and concentrated under reduced pressure to yield a residue. The residue was purified on a silica gel ISCO cartridge with elution at 0 to 15% EtOAc/hexane to give 2,2-bis(3-(trifluoromethoxy)phenyl)acetonitrile (6.7 g, 67% yield) as a clear yellow oil. LCMS: RT=3.90 min [M−H] 360.2 (2 min Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% NH4OAc; 4 mL/min, monitoring at 220 nm); NMR: 400 MHz 1H (CDCl3) ppm 5.18 (s, 1 H), 7.18 (s, 2 H), 7.24 (d, J=9.67 Hz, 2 H), 7.30 (d, J=7.91 Hz, 2 H), 7.46 (t, J=7.91 Hz, 2 H).

1. temperatureThe reaction mixture was cooled in an ice-bath
2. additionUpon completion of addition
3. customthe ice-bath was removed
4. stirringthe reaction mixture was stirred for an additional hour
5. extractionextracted with hexane (3×200 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto yield a residue
10. customThe residue was purified on a silica gel ISCO cartridge with elution at 0 to 15% EtOAc/hexane

ORD record

ord-04d359d1108049829f091e88ceb5f144

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08404896B2