Hydrochloric Acid → Methyl 7-chloroisoquinoline-3-carboxylate

HRID 546496Notes

Reaction equation

HRID 546496 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C@H:4]([CH3:15])[N:5]([C:8]1[CH:13]=[CH:12][C:11](Cl)=[CH:10]C=1)C=O.[C:17](Cl)(=O)C(Cl)=O.Cl.Cl[CH2:25][Cl:26]>>[Cl:26][C:25]1[CH:17]=[C:13]2[C:12]([CH:15]=[C:4]([C:3]([O:2][CH3:1])=[O:16])[N:5]=[CH:8]2)=[CH:11][CH:10]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 6344Dichloromethane2×HCID 65578Oxalyl chlorideHCID 18442857(+/-)-N-Formyl-(4-chlorophenyl)alanine methyl ester

Product 1

HCID 17842489Methyl 7-chloroisoquinoline-3-carboxylate

Procedure

(±)-N-Formyl-(4-chlorophenyl)alanine methyl ester (1.45 g) was dissolved in dichloromethane (40 ml), and oxalyl chloride (0.57 ml) was added dropwise. After the mixture was stirred at room temperature for 30 minutes, ferric chloride (1.17 g) was added at an ambient temperature of about −10° C. to stir the mixture at room temperature for 4 days. 1N Hydrochloric acid was added, and the resultant mixture was diluted with dichloromethane to separate an organic layer. The organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was dissolved in methanol (38 ml), and concentrated sulfuric acid (2 ml) was added to heat the mixture for 20 hours under reflux. An aqueous solution of sodium hydrogencarbonate was added to the reaction mixture, the resultant mixture was extracted with dichloromethane, and the extract was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1→ethyl acetate) to obtain the title compound (0.25 g) as colorless crystals.

Workup

  1. stirringto stir the mixture at room temperature for 4 days
  2. customto separate an organic layer
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. dissolutionthe residue was dissolved in methanol (38 ml)
  6. additionconcentrated sulfuric acid (2 ml) was added
  7. temperatureto heat the mixture for 20 hours
  8. temperatureunder reflux
  9. additionAn aqueous solution of sodium hydrogencarbonate was added to the reaction mixture
  10. extractionthe resultant mixture was extracted with dichloromethane
  11. dry with materialthe extract was dried over anhydrous sodium sulfate
  12. distillationThe solvent was distilled off under reduced pressure
  13. customthe residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1→ethyl acetate)

Sources & evidence

ORD record
ord-196764322e6e413fa94ce1bddbdc3081
Source dataset
uspto-grants-2011_05
Patent number
US07935824B2

Reaction notes

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