Sodium hydride → [3-Benzyl-8-(trifluoromethyl)quinolin-4-yl](3-methoxyphenyl)acetonitrile

HRID 2104797Notes

Reaction equation

HRID 2104797 reaction equation
[CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1Br)=[CH:15][CH:14]=[CH:13][C:12]=2[C:19]([F:22])([F:21])[F:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:23][O:24][C:25]1[CH:26]=[C:27]([CH2:31][C:32]#[N:33])[CH:28]=[CH:29][CH:30]=1.[H-].[Na+]>C1COCC1.O>[CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[CH:31]([C:27]1[CH:28]=[CH:29][CH:30]=[C:25]([O:24][CH3:23])[CH:26]=1)[C:32]#[N:33])=[CH:15][CH:14]=[CH:13][C:12]=2[C:19]([F:22])([F:21])[F:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 88310(3-Methoxyphenyl)acetonitrileHCID 669131463-Benzyl-4-bromo-8-(trifluoromethyl)quinoline

Product 1

HCID 66913948[3-Benzyl-8-(trifluoromethyl)quinolin-4-yl](3-methoxyphenyl)acetonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A stirred mixture of 3-benzyl-4-bromo-8-(trifluoromethyl)quinoline (10.0 g, 27.31 mmol) and (3-methoxyphenyl)acetonitrile (5.57 mL, 40.96 mmol) in THF (100 mL) is treated with NaH (1.64 g, 41.0 mmol, 60% dispersion in oil). After 0.5 h at ambient temperature, the reaction is heated at 50° C. for 2 h. The cooled reaction is diluted with water, extracted with ethyl acetate, and the combined extracts are dried (MgSO4) and concentrated. The residue is purified via column chromatography using 10:90 ethyl acetate:hexane as the eluent. The purified product is dissolved in a mixture of methylene chloride and hexane and concentrated until precipitation commences. After precipitation is complete, [3-benzyl-8-(trifluoromethyl)quinolin-4-yl](3-methoxyphenyl)acetonitrile is isolated as an off-white crystalline solid (5.18 g, 44%). HRMS: calcd for C26H19F3N2O+H+, 433.15222; found (ESI, [M+H]+), 433.1528.

Workup

  1. customThe cooled reaction
  2. extractionextracted with ethyl acetate
  3. dry with materialthe combined extracts are dried (MgSO4)
  4. concentrationconcentrated
  5. customThe residue is purified via column chromatography
  6. dissolutionThe purified product is dissolved in a mixture of methylene chloride and hexane
  7. concentrationconcentrated until precipitation commences
  8. customAfter precipitation

Sources & evidence

ORD record
ord-92eafc4da957489699818ce15b5ea918
Source dataset
uspto-grants-2009_08
Patent number
US07576215B2

Reaction notes

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