Acetic Acid → 3-(1,1-difluoroethyl)benzaldehyde

HRID 1969449Notes

Reaction equation

HRID 1969449 reaction equation
[F:1][C:2]([C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][CH:12]=1)[C:8]#N)([F:4])[CH3:3].[H-].C([Al+]CC(C)C)C(C)C.C(=O)=[O:24].CC(O)=O>C1(C)C=CC=CC=1.O>[F:1][C:2]([C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][CH:12]=1)[CH:8]=[O:24])([F:4])[CH3:3]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 280Carbon DioxideHCID 21225700DiisobutylaluminumhydrideHCID 222616813-(1,1-Difluoroethyl)benzonitrile

Product 1

HCID 574716373-(1,1-difluoroethyl)benzaldehyde

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
-78 °C

Procedure

Dissolve 3-(1,1-difluoro-ethyl)-benzonitrile (4.39 g, 26.26 mmol) in toluene (44 mL). Place the reaction under nitrogen, cool to −78° C. in a dry-ice bath, then add diisobutylaluminum hydride (52.5 mmol, 1 M solution in toluene) dropwise over 30 minutes with stirring. Stir the reaction in the dry-ice bath for 30 minutes, then add glacial HOAc (14 mL) dropwise to control foaming, followed by water (100 mL). Stir the reaction mixture overnight at room temperature. Separate the layers; extract the cloudy aqueous with toluene. Wash the toluene extracts with brine, dry the organics over magnesium sulfate, filter, and evaporate to afford 3-(1,1-difluoro-ethyl)-benzaldehyde as a pale yellow oil. (4.0 g, 90%). 1H NMR (400 MHz, CDCl3): δ 10.03 (s, 1H), 8.00 (s, 1H), 7.92 (d, J=7.5 Hz, 1H), 7.75 (d, J=7.5 Hz, 1H), 7.58 (t, J=7.7 Hz, 1H), 1.98-1.89 (m, 3H).

Workup

  1. customthe reaction under nitrogen
  2. stirringStir the reaction mixture overnight at room temperature
  3. customSeparate the layers
  4. extractionextract the cloudy aqueous with toluene
  5. washWash the toluene
  6. dry with materialdry the organics over magnesium sulfate
  7. filtrationfilter
  8. customevaporate

Sources & evidence

ORD record
ord-9198519df8084be299b5770a23d950f6
Source dataset
uspto-grants-2013_04
Patent number
US08426448B2

Reaction notes

Loading…