Hydrochloric Acid → 6-Chloro-5-fluoroindolin-2-one

HRID 4470

Reaction equation

HRID 4470 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].Cl.Cl[CH2:7][C:8]([NH:10][C:11]1[CH:16]=[CH:15][C:14]([F:17])=[C:13]([Cl:18])[CH:12]=1)=[O:9]>>[Cl:18][C:13]1[CH:12]=[C:11]2[C:16]([CH2:7][C:8](=[O:9])[NH:10]2)=[CH:15][C:14]=1[F:17]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 7358492-chloro-N-(3-chloro-4-fluorophenyl)acetamideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 97940836-Chloro-5-fluoroindolin-2-oneYield 7%

Procedure

A 26.63 g. sample of the N-(2-chloro)-2-chloro-4-fluoroaniline was thoroughly mixed with 64 g. of anhydrous aluminum chloride, and the mixture was heated at 210°-230° C. for 8.5 hours. The reaction mixture was then poured onto a mixture of ice an 1N hydrochloric acid, with stirring. Stirring was continued for 30 minutes, and then the solid was collected by filtration (22.0 g.). The solid was dissolved in 1:1 ethyl acetate-hexane and chromatographed on 800 g. of silica gel. Elution of the column, followed by evaporation of the fractions, produced 11.7 g. of the N-(2-chloroacetyl)-3-chloro-4-fluoroaniline, followed by 3.0 g. of 6-chloro-5-fluorine-2-oxindole. The latter material was recrystallized from toluene to give 1.70 g. (7% yield) of the title compound, m.p. 196°-206° C. Analysis by NMR spectroscopy indicated that the product was contaminated by some 4-chloro-5-fluorooxindole. A second crop weighing 0.8 g. was obtained.

Workup

  1. stirringStirring
  2. filtrationthe solid was collected by filtration (22.0 g.)
  3. dissolutionThe solid was dissolved in 1:1 ethyl acetate-hexane
  4. customchromatographed on 800 g
  5. washElution of the column
  6. customfollowed by evaporation of the fractions
  7. customproduced 11.7 g
  8. customThe latter material was recrystallized from toluene
  9. customto give 1.70 g

Sources & evidence

ORD record
ord-648f109ece9742c68f0c921925e57cde
Source dataset
uspto-grants-1988_02
Patent number
US04725616

Linked notes

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