Hydrochloric Acid → 1-(4-tert-Butylphenyl)-2-carboxymethyl-5-(5-carboxypyridin-2-yloxy)-6-chloroindole-3-carboxylic acid

HRID 420946Notes

Reaction equation

HRID 420946 reaction equation
C([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][C:11]([Cl:27])=[C:12]([O:15][C:16]3[CH:21]=[CH:20][C:19]([C:22](=[O:26])N(C)C)=[CH:18][N:17]=3)[CH:13]=2)[N:8]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:30][CH:29]=2)[C:7]=1[CH2:38][C:39]([O:41]CC)=[O:40])=[O:5])C.[OH-:44].[Na+].Cl>O1CCOCC1>[C:34]([C:31]1[CH:30]=[CH:29][C:28]([N:8]2[C:9]3[C:14](=[CH:13][C:12]([O:15][C:16]4[CH:21]=[CH:20][C:19]([C:22]([OH:26])=[O:44])=[CH:18][N:17]=4)=[C:11]([Cl:27])[CH:10]=3)[C:6]([C:4]([OH:3])=[O:5])=[C:7]2[CH2:38][C:39]([OH:41])=[O:40])=[CH:33][CH:32]=1)([CH3:35])([CH3:36])[CH3:37]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 666575291-(4-tert-Butylphenyl)-6-chloro-5-(5-dimethylcarbamoyl-pyridin-2-yloxy)-2-ethoxycarbonylmethylindole-3-carboxylic acid ethyl ester

Product 1

HCID 666576071-(4-tert-Butylphenyl)-2-carboxymethyl-5-(5-carboxypyridin-2-yloxy)-6-chloroindole-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 1-(4-tert-butylphenyl)-6-chloro-5-(5-dimethylcarbamoyl-pyridin-2-yloxy)-2-ethoxycarbonylmethylindole-3-carboxylic acid ethyl ester (124 mg, 4.07 mmol; see step (c) above), NaOH (aq, 2 M, 1.0 mL) and dioxane (2.0 mL) was heated at reflux for 48 h, cooled, acidified to pH 2 with HCl (aq, 1 M) and extracted with EtOAc. The combined extracts were washed with H2O and brine, dried (Na2SO4), concentrated and purified by chromatography to give the title compound. Yield 40 mg (36%), mp 223-235° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 48 h
  3. temperaturecooled
  4. extractionextracted with EtOAc
  5. washThe combined extracts were washed with H2O and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. custompurified by chromatography

Sources & evidence

ORD record
ord-b09742d3a8a84a2da8cc7877462e1e13
Source dataset
uspto-grants-2012_01
Patent number
US08097623B2

Reaction notes

Loading…