Benzeneacetonitrile, 4-fluoro- → HCID 86716206, compound

HRID 512179Notes

Reaction equation

HRID 512179 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.CC([O-])(C)C.[K+].Br[C:18]1[CH:19]=[CH:20][C:21]([C:24]([F:27])([F:26])[F:25])=[N:22][CH:23]=1>COCCOC>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:18]2[CH:23]=[N:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=2)[C:9]#[N:10])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 68016Benzeneacetonitrile, 4-fluoro-HCID 27611975-Bromo-2-(trifluoromethyl)pyridineHCID 23665647Potassium tert-butoxide

Product 1

HCID 86716206HCID 86716206, compoundYield 434%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of 2-(4-fluorophenyl)acetonitrile (2 g, 14.8 mmol) in DME (50 mL) was degassed. KOtBu (6.63 g, 59.2 mmol) was added in portions. After addition was completed, the mixture was stirred for 5 min at room temperature and a brown suspension was formed. Then 5-bromo-2-(trifluoromethyl)pyridine (6.69 g, 29.6 mmol) was added followed by Pf(dppf)Cl2 (1.35 g, 1.48 mmol). The resulting mixture was heated to 60° C. for 4 h. The reaction mixture was cooled to room temperature and quenched by aq. NH4Cl to pH=5˜6. The mixture was extracted with EtOAc (50 mLx3). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash combi (Petroleum ether/EtOAc=15:1) to give 2-(4-fluorophenyl)-2-(6-(trifluoromethyl)pyridin-3-yl)acetonitrile (18 g, ˜70% purity +350 mg, pure, yield: 51.8%). 1H NMR (CDCl3 400 MHz) c58.98 (s, 1H), 7.89 (dd, J=8.4, 2.4 Hz, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.40-7.30 (m, 2H), 7.20-7.10 (m, 2H), 5.26 (s, 1H).

Workup

  1. additionAfter addition
  2. customa brown suspension was formed
  3. temperatureThe resulting mixture was heated to 60° C. for 4 h
  4. temperatureThe reaction mixture was cooled to room temperature
  5. customquenched by aq. NH4Cl to pH=5˜6
  6. extractionThe mixture was extracted with EtOAc (50 mLx3)
  7. washThe combined organic layer was washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customThe residue was purified by flash combi (Petroleum ether/EtOAc=15:1)

Sources & evidence

ORD record
ord-58b5d0148f6d4758bf138632afca87ec
Source dataset
uspto-grants-2015_08
Patent number
US09102591B2

Reaction notes

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