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

HRID 237276Notes

Reaction equation

HRID 237276 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[CH:3]=1.C([Li])CCC.CN([CH:18]=[O:19])C.Cl>C1COCC1.CCOCC>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([CH:18]=[O:19])=[C:4]([F:9])[CH:3]=1

Participants

7

Reactant 4

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

Product 1

HCID 27735124-Chloro-2,6-difluorobenzaldehydeYield 41.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a −78° C. solution of 1-chloro-3,5-difluoro-benzene (5.0 g, 34 mmol) in THF (70 mL) at was added n-butyl lithium (1.6 M in hexane, 19 mL). After 50 min, DMF (5.2 mL, 67 mmol) was added and the reaction was allowed to warm to rt over 18 h. After the addition of 0.5 M HCl (150 mL) and ether (150 mL), the aqueous layer was extracted with Et2O (3×). The combined organic extracts were dried and concentrated to provide a yellow solid. The crude material was dissolved in warm hexanes and a small amount of white solid formed upon cooling. This white solid was filtered off and discarded. The filtrate was concentrated to provide the title compound as a light yellow solid (2.5 g, 41%). 1H NMR (CDCl3): 10.3 (s, 1H), 7.06 (d, J=8.1 Hz, 2H).

Workup

  1. extractionthe aqueous layer was extracted with Et2O (3×)
  2. customThe combined organic extracts were dried
  3. concentrationconcentrated
  4. customto provide a yellow solid
  5. customa small amount of white solid formed
  6. temperatureupon cooling
  7. filtrationThis white solid was filtered off
  8. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-c6093fe16b204cbb9a556da9485be587
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

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