Sodium Hydroxide → N-(3-methoxy-4-chlorobenzyl)-5-hydroxyindole-2-carboxylic Acid

HRID 1610924Notes

Reaction equation

HRID 1610924 reaction equation
[OH-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]([CH:27]=[CH:28][C:29]=1[Cl:30])[CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([O:18]C(=O)C)=[CH:15][CH:16]=2)[CH:11]=[C:10]1[C:22]([O:24]CC)=[O:23]>CO.C1COCC1>[CH3:3][O:4][C:5]1[CH:6]=[C:7]([CH:27]=[CH:28][C:29]=1[Cl:30])[CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([OH:18])=[CH:15][CH:16]=2)[CH:11]=[C:10]1[C:22]([OH:24])=[O:23]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 22259373Ethyl 5-acetoxy-N-(3-methoxy-4-chlorobenzyl)indole-2-carboxylate

Product 1

HCID 9927559N-(3-methoxy-4-chlorobenzyl)-5-hydroxyindole-2-carboxylic AcidYield 70.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydroxide (2M, 1.9 ml) was added to a stirred solution of ethyl N-(3-methoxy-4-chlorobenzyl)-5-acetoxyindole-2-carboxylate (305 mg) in methanol (3 ml) and THF (3 ml). The reaction was stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo and then diluted with water (5 ml). The solution was acidified by the addition of aqueous hydrochloric acid (2M), extracted with ethyl acetate, dried and evaporated. The residue was purified by column chromatography eluting 20%-100% ethyl acetate to give the desired product as a solid (177 mg, 70%) NMR (CD3SOCD3): d 3.95 (s, 3H), 5.95 (s, 2H), 6.35 (d, 1H), 6.8 (dd, 1H), 6.9 (d, 1H), 7.0 (d, 1 μl), 7.1 (s, 1H), 7.25 (d, 1H), 7.3 (d, 1H), 9.0 (s, 1H); m/z 332 (M+H+).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiondiluted with water (5 ml)
  3. additionThe solution was acidified by the addition of aqueous hydrochloric acid (2M)
  4. extractionextracted with ethyl acetate
  5. customdried
  6. customevaporated
  7. customThe residue was purified by column chromatography
  8. washeluting 20%-100% ethyl acetate

Sources & evidence

ORD record
ord-c67ac137f55f4692a3d6391890974778
Source dataset
uspto-grants-2006_01
Patent number
US06984657B1

Reaction notes

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