Benzyl Bromide → 3-Phenyl-2,2-bis(3-(trifluoromethoxy)phenyl)propanenitrile

To a solution of diisopropyl amine (2.48 mL, 17.5 mmol) in THF (60 mL) at −78° C. was added dropwise n-BuLi (1.6 M in hexane, 11.5 mL, 18.3 mmol) and the reaction mixture was stirred for 5 min. A solution of (2,2-bis(3-(trifluoromethoxy)phenyl)acetonitrile (5.51 g, 15.3 mmol), prepared as described in Procedure 14, in THF (5 mL) was added dropwise to the reaction mixture and stirred for 1h. Benzyl bromide (2.17 mL, 18.3 mmol) was added dropwise, then the cooling bath was removed and the reaction mixture was stirred at rt for 45 min. The reaction mixture was poured into H2O (75 mL) and extracted with diethyl ether (2×75 mL). The combined organic portions were 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 5 to 15% Et2O/hexane to give 3-phenyl-2,2-bis(3-(trifluoromethoxy)phenyl)propanenitrile (6.75 g, 98% yield) as a clear yellow oil. LCMS: RT=2.18 min [M-CN] 425.1 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); NMR: 400 MHz 1H(CDCl3) ppm 3.63 (s, 2 H), 6.87 (d, J=7.03 Hz, 2 H), 7.15-7.26 (m, 9 H), 7.40 (t, J=8.13 Hz, 2 H).

1. additionwas added dropwise to the reaction mixture
2. stirringstirred for 1h
3. customthe cooling bath was removed
4. stirringthe reaction mixture was stirred at rt for 45 min
5. additionThe reaction mixture was poured into H2O (75 mL)
6. extractionextracted with diethyl ether (2×75 mL)
7. dry with materialThe combined organic portions were dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto yield a residue
11. customThe residue was purified on a silica gel ISCO cartridge with elution at 5 to 15% Et2O/hexane

ORD record

ord-21a762d6a13341d5bfbd6ea6294207ca

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09102599B2