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

HRID 511936Notes

Reaction equation

HRID 511936 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[F:13][C:14]([F:37])([F:36])[O:15][C:16]1[CH:17]=[C:18]([CH:22]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([O:31][C:32]([F:35])([F:34])[F:33])[CH:26]=2)[C:23]#[N:24])[CH:19]=[CH:20][CH:21]=1.[CH2:38](Br)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C1COCC1>[C:39]1([CH2:38][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([O:31][C:32]([F:35])([F:34])[F:33])[CH:26]=2)([C:18]2[CH:19]=[CH:20][CH:21]=[C:16]([O:15][C:14]([F:36])([F:37])[F:13])[CH:17]=2)[C:23]#[N:24])[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

6

Reactant 4

HCID 7498Benzyl BromideHCID 7912DiisopropylamineHCID 594587512,2-Bis(3-(trifluoromethoxy)phenyl)acetonitrileHCID 178418339Butyllithium

Product 1

HCID 591928133-Phenyl-2,2-bis(3-(trifluoromethoxy)phenyl)propanenitrileYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-21a762d6a13341d5bfbd6ea6294207ca
Source dataset
uspto-grants-2015_08
Patent number
US09102599B2

Reaction notes

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