Acetic Acid → 2-Chloro-4-(trifluoromethyl)benzaldehyde

HRID 1021456Notes

Reaction equation

HRID 1021456 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=1[C:4]#N.CC(C[AlH]CC(C)C)C.C(O)(=[O:25])C.O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:25]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 14487Diisobutylaluminum hydrideHCID 27364762-Chloro-4-(trifluoromethyl)benzonitrile

Product 1

HCID 130761442-Chloro-4-(trifluoromethyl)benzaldehydeYield 78.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-78 °C

Procedure

2-Chloro-4-(trifluoromethyl)benzonitrile (500 mg, 2.43 mmol) was diluted with toluene (3 mL), placed under nitrogen and cooled to −78° C. DIBAL-H (4865 μL, 4.86 mmol) was added dropwise and the reaction was stirred for 1 hour. The reaction was warmed to 0° C. and acetic acid (2 mL) was added followed by 10 mL of water. After stirring for 2 hours, the reaction was extracted twice with ethyl acetate, washed with Rochelle's salt, dried over MgSO4, filtered and concentrated. The material was purified using a biotage 25 cartridge running a gradient, 100% hexanes to 20% DCM/hexanes to yield 2-chloro-4-(trifluoromethyl)benzaldehyde (400 mg, 1.92 mmol, 78.8% yield) as a clear oil.

Workup

  1. temperatureThe reaction was warmed to 0° C.
  2. stirringAfter stirring for 2 hours
  3. extractionthe reaction was extracted twice with ethyl acetate
  4. washwashed with Rochelle's salt
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was purified

Sources & evidence

ORD record
ord-5d89f3c3a4464dfcae77f8b5cac99077
Source dataset
uspto-grants-2014_05
Patent number
US08716498B2

Reaction notes

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