Hydrochloric Acid → 4-Chloro-2,6-difluorobenzaldehyde

HRID 1266367Notes

Reaction equation

HRID 1266367 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([Cl:9])[CH:5]=[C:6]([F:8])[CH:7]=1.C([Li])CCC.CCCCCC.CN(C)[CH:23]=[O:24].Cl>O1CCCC1.CCOCC>[Cl:9][C:4]1[CH:3]=[C:2]([F:1])[C:7]([CH:23]=[O:24])=[C:6]([F:8])[CH:5]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 8058HexaneHCID 137000Benzene, 1-chloro-3,5-difluoro-HCID 178418339Butyllithium

Product 1

HCID 27735124-Chloro-2,6-difluorobenzaldehydeYield 96%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3,5-difluoro-1-chlorobenzene (5.0 g, 34 mmol) in tetrahydrofuran (70 mL) at −78° C. was added a solution of n-butyllithium in hexane (12.1 mL, 2.5 M, 30 mmol). After stirring for 1 hour, dimethylformamide (5.2 mL, 67 mmol) was added, and the mixture was stirred for 1.5 hours. The mixture was warmed to ambient temperature, diluted with ether and poured into 150 mL of 0.5 M aqueous HCl. The aqueous phase was extracted 3× into ether, and the combined organic layers were dried over MgSO4, filtered and concentrated in vacuo, affording 5.72 g (96%) of 4-chloro-2,6-difluoro-benzaldehyde as a colorless solid. 1H NMR (400 MHz, CDCl3) δ 10.27 (s, 1H), 7.04 (d, 2H, J=7.9 Hz) ppm.

Workup

  1. stirringthe mixture was stirred for 1.5 hours
  2. extractionThe aqueous phase was extracted 3× into ether
  3. dry with materialthe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-574724e4529c4c759295f2f34a6fb260
Source dataset
uspto-grants-2003_04
Patent number
US06548526B2

Reaction notes

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