Diethyl Ether → 3-(1,1-difluoroethyl)benzaldehyde

HRID 1919806Notes

Reaction equation

HRID 1919806 reaction equation
[F:1][C:2]([C:5]1[CH:6]=[C:7]([CH2:11][OH:12])[CH:8]=[CH:9][CH:10]=1)([F:4])[CH3:3].C(OCC)C.C(=O)(O)[O-].[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>ClCCl>[F:1][C:2]([C:5]1[CH:6]=[C:7]([CH:8]=[CH:9][CH:10]=1)[CH:11]=[O:12])([F:4])[CH3:3]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 24477Sodium ThiosulfateHCID 516892Sodium BicarbonateHCID 574463343-(1,1-difluoroethyl)- Benzenemethanol

Product 1

HCID 574716373-(1,1-difluoroethyl)benzaldehydeYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Add a solution of [3-(1,1-Difluoro-ethyl)-phenyl]-methanol (3.47 mmol) in dichloromethane (10.5 mL) dropwise to a suspension of 3,3,3-triacetoxy-3-iodophthalide (3.64 mmol) in dichloromethane (10.5 mL) at room temperature. Stir for 30 minutes. Add diethyl ether (10 mL) and 5% aqueous sodium bicarbonate (10 mL) containing sodium thiosulfate (3 g). Mix well for 20 minutes. Separate the layers, and extract the aqueous with ethyl ether. Combine the organic layers, wash with brine, dry over sodium sulfate, filter, and evaporate to give a yellow solid. Purify over silica (40 g) eluting with 0 to 50% dichloromethane in hexanes. Evaporate until most solvent is removed being careful not to drive off the volatile product. Dry additionally by blowing a nitrogen stream over the product to give the title compound in 70% yield. 1HNMR (400.43 MHz, CDCl3): δ 10.03 (s, 1H), 8.00 (s, 1H), 7.92 (d, J=7.5 Hz, 1H), 7.75 (d, J=7.0 Hz, 1H), 7.59 (t, J=7.7 Hz, 1H), 1.98-1.89 (m, 3H).

Workup

  1. additionMix well for 20 minutes
  2. customSeparate the layers
  3. extractionextract the aqueous with ethyl ether
  4. washwash with brine
  5. dry with materialdry over sodium sulfate
  6. filtrationfilter
  7. customevaporate
  8. customto give a yellow solid
  9. customPurify over silica (40 g)
  10. washeluting with 0 to 50% dichloromethane in hexanes
  11. customEvaporate until most solvent
  12. customis removed
  13. customDry additionally

Sources & evidence

ORD record
ord-31b20f2f9bbf489f9eea32d20dfff4f1
Source dataset
uspto-grants-2012_05
Patent number
US08168659B2

Reaction notes

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