Dimethylformamide → 3-(Hydroxymethyl)-5-(trifluoromethyl)benzonitrile

HRID 391407Notes

Reaction equation

HRID 391407 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:12][OH:13])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH3:14][N:15](C)C=O>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C-]#N.[Zn+2].[C-]#N>[OH:13][CH2:12][C:4]1[CH:3]=[C:2]([CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=1)[C:14]#[N:15]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 29919767[3-Bromo-5-(trifluoromethyl)phenyl]methanol

Product 1

HCID 117012213-(Hydroxymethyl)-5-(trifluoromethyl)benzonitrile

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Procedure

(3-Bromo-5-(trifluoromethyl)phenyl)methanol (1.4 g, 5.5 mmol), tetrakis(triphenylphosphine) palladium(0) (0.64, 0.55 mmol) and zinc cyanide (388 mg, 3.31 mmol) were combined in dimethylformamide (6 mL). The reaction mixture degassed repeatedly using the freeze-thaw method. After warming to room temperature, the reaction was heated at 90° C. for 1 h, cooled to room temperature and concentrated. The crude product was dissolved in ethyl acetate, washed with water (2×), 1 N hydrochloric acid (2×), brine (2×), dried over sodium sulfate, and concentrated. Flash chromatography on silica gel gave 0.37 g (33%). LC/MS (HPLC method 3): tR=2.06 min, 202.02 (MH)+.

Workup

  1. customThe reaction mixture degassed repeatedly
  2. temperaturethe reaction was heated at 90° C. for 1 h
  3. temperaturecooled to room temperature
  4. concentrationconcentrated
  5. dissolutionThe crude product was dissolved in ethyl acetate
  6. washwashed with water (2×), 1 N hydrochloric acid (2×), brine (2×)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customFlash chromatography on silica gel gave 0.37 g (33%)

Sources & evidence

ORD record
ord-2434f595a78d4ca38fa68bbdbd39bf82
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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