Hydrochloric Acid → HCID 10644711, compound

HRID 1069576Notes

Reaction equation

HRID 1069576 reaction equation
C([O:3][C:4](=[O:30])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]([Cl:25])=[C:12]2[CH2:26][C:27]([NH2:29])=[O:28])C.[OH-].[Na+].Cl>CCO>[NH2:29][C:27](=[O:28])[CH2:26][C:12]1[C:11]2[C:15](=[CH:16][CH:17]=[C:9]([O:8][CH2:7][CH2:6][CH2:5][C:4]([OH:30])=[O:3])[CH:10]=2)[N:14]([CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:13]=1[Cl:25]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 10574582HCID 10574582, compound

Product 1

HCID 10644711HCID 10644711, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 140 mg (0.43 mmol) of 2-chloro-5-methoxy-1-(phenylmethyl)-1H-indole-3-acetamide (Example 11) in 20 mL of methylene chloride was treated with 2 mL of 1M BBr3/CH2Cl2, stirred for 1.5 hours, stirred with aqueous HCl, the CH2Cl2 solvent separated, and washed with water, saturated NaCl solution and dried (Na2SO4). On concentrating at reduced pressure, there was obtained 140 mg of crude 2-chloro-5-hydroxy-1-(phenylmethyl)-1H-indole-3-acetamide. This material was dissolved in 15 mL of DMSO, 20 mg of 60% NaH/mineral oil added, and after 5 minutes, 0.1 mL of ethyl 4-bromobutyrate was added. The reaction mixture was heated by oil bath at 70° C. for 70 minutes. After cooling, the mixture was diluted with water, extracted with EtOAc, the EtOAc solution washed with water, saturated NaCl solution and dried (Na2SO4). After concentrating, a residue was obtained that was chromatographed on silca (eluted with CH2Cl2→3% MeOH/CH2Cl2) to give 105 mg of 4-[[3-(2-amino-2-oxoethyl)-2-chloro-1-(phenylmethyl)-1H-indole-5-yl]oxy]butanoic acid ethyl ester. This ester (105 mg) was dissolved in 15 mL of EtOH, 1 mL of 5N NaOH added, and the solution stirred for 18 hours. The mixture was made acidic with 5N HCl, and extracted with EtOAc. The EtOAc solution was washed with saturated NaCl solution, dried (Na2SO4) and concentrated at reduced pressure. The residue was dissolved in MeOH/CH2Cl2, the solution concentrated, to give 75 mg (80% yield) of 4-[[3-(2-amino-2-oxoethyl)-2-chloro-1-(phenylmethyl)-1H-indol-5-yl]oxy]butanoic acid, mp, 198-200° C.

Workup

  1. extractionextracted with EtOAc
  2. washThe EtOAc solution was washed with saturated NaCl solution
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated at reduced pressure
  5. dissolutionThe residue was dissolved in MeOH/CH2Cl2
  6. concentrationthe solution concentrated

Sources & evidence

ORD record
ord-ca4e42345bad4340a5ea5ab55b257fa7
Source dataset
uspto-grants-2001_06
Patent number
US06252084B1

Reaction notes

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