Hydrochloric Acid → 4-Amino-2-chloro-3-fluorobenzaldehyde

HRID 501635Notes

Reaction equation

HRID 501635 reaction equation
Cl[C:2]1[C:3]([F:9])=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[ClH:10].[OH-:11].[Na+].[CH3:13]S(C)=O>O.[Cu](Cl)Cl>[NH2:5][C:4]1[CH:6]=[CH:7][C:8]([CH:13]=[O:11])=[C:2]([Cl:10])[C:3]=1[F:9]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 679Dimethyl SulfoxideHCID 14798Sodium HydroxideHCID 750143-Chloro-2-fluoroaniline

Product 1

HCID 597543024-Amino-2-chloro-3-fluorobenzaldehyde

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To 3-chloro-2-fluoroaniline (10.0 g, 68.7 mmol) in DMSO (500 mL) was added copper (II) chloride (18.5 g, 137.4 mmol) and conc. HCl (50 mL). The whole was heated to 90° C. for 13 h. The reaction was cooled to 0° C. and 4N NaOH was added dropwise to adjust to pH 8. The reaction was diluted with water and extracted with Et2O/EtOAc (1:1). The organic layer was washed with brine, and was dried, filtered and concentrated. The resulting residue was purified via silica gel chromatography eluting with 5-30% EtOAc/hexane to provide 4-amino-2-chloro-3-fluorobenzaldehyde (100 g) as a yellow powder.

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. extractionextracted with Et2O/EtOAc (1:1)
  3. washThe organic layer was washed with brine
  4. customwas dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified via silica gel chromatography
  8. washeluting with 5-30% EtOAc/hexane

Sources & evidence

ORD record
ord-645af9727da54125be5e5c3fcc40c32d
Source dataset
uspto-grants-2010_08
Patent number
US07772267B2

Reaction notes

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