Hydrochloric Acid → 6-chloro-5-(3,4-dimethoxyphenyl)-1H-indole-3-carboxylic acid

HRID 338320Notes

Reaction equation

HRID 338320 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13]C)=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([O:23][CH3:24])[CH:16]=1.CO.[OH-].[Na+].Cl>C(OCC)(=O)C.C(Cl)Cl>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:13])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([O:23][CH3:24])[CH:16]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887Methanol2×HCID 14798Sodium HydroxideHCID 86698666methyl 6-chloro-5-(3,4-dimethoxyphenyl)-1H-indole-3-carboxylate

Product 1

HCID 866986676-chloro-5-(3,4-dimethoxyphenyl)-1H-indole-3-carboxylic acidYield 24%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl 6-chloro-5-(3,4-dimethoxyphenyl)-1H-indole-3-carboxylate (75 mg, 0.22 mmol), methanol (2.2 mL), and aqueous sodium hydroxide (1M, 0.75 mL, 0.75 mmol) was heated at 75° C. for 24 hours. The reaction was acidified with 1M HCl to pH=2 then diluted with ethyl acetate. The aqueous layer was back-extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to provide a crude solid. The crude product was dissolved in methylene chloride and methanol and silica gel was added. The solvent was removed in vacuo and the crude material adsorbed onto silica was loaded onto a column of silica gel and eluted with ethyl acetate (with 0.2% formic acid)/heptanes (1:1 to 1:0) to provide the title compound (17 mg, 24%) as a tan solid.

Workup

  1. extractionThe aqueous layer was back-extracted twice with ethyl acetate
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto provide a crude solid
  6. customThe solvent was removed in vacuo
  7. washeluted with ethyl acetate (with 0.2% formic acid)/heptanes (1:1 to 1:0)

Sources & evidence

ORD record
ord-42f33efa79e1451395cc522a2a7331af
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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