Sodium Hydroxide → 3-(3,4-Difluorobenzylcarbamoyl)-6-isopropoxy-1-(pyridin-2-ylmethyl)-1H-indole-2-carboxylic Acid

HRID 40103Notes

Reaction equation

HRID 40103 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:35]=[CH:36][C:37]=1[F:38])[CH2:5][NH:6][C:7]([C:9]1[C:17]2[C:12](=[CH:13][C:14]([O:18][CH:19]([CH3:21])[CH3:20])=[CH:15][CH:16]=2)[N:11]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)[C:10]=1[C:29]([O:31]C(C)C)=[O:30])=[O:8].[OH-].[Na+]>CO>[F:1][C:2]1[CH:3]=[C:4]([CH:35]=[CH:36][C:37]=1[F:38])[CH2:5][NH:6][C:7]([C:9]1[C:17]2[C:12](=[CH:13][C:14]([O:18][CH:19]([CH3:21])[CH3:20])=[CH:15][CH:16]=2)[N:11]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)[C:10]=1[C:29]([OH:31])=[O:30])=[O:8]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 69226775HCID 69226775, compound2×

Product 1

HCID 597624513-(3,4-Difluorobenzylcarbamoyl)-6-isopropoxy-1-(pyridin-2-ylmethyl)-1H-indole-2-carboxylic Acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of isopropyl 3-(3,4-difluorobenzylcarbamoyl)-6-isopropoxy-1-(pyridin-2-ylmethyl)-1H-indole-2-carboxylate (Compound 101, 551 mg, 1.06 mmol) in MeOH (15 ml) and NaOH (1 M, 5.3 ml, 5.3 mmol) was stirred at room temperature for 4 h. The reaction was quenched cautiously with 6 M HCl at 0° C., extracted with EtOAc (×3). The combined organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel (EtOAc, then 8:2 EtOAc-MeOH, then 7:2:1 EtOAc-MeOH-Et3N) to yield the title compound as its Et3N salt.

Workup

  1. customThe reaction was quenched cautiously with 6 M HCl at 0° C.
  2. extractionextracted with EtOAc (×3)
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by chromatography on silica gel (EtOAc

Sources & evidence

ORD record
ord-a17622cf4fbd4e8a8e223f0e06205591
Source dataset
uspto-grants-2013_09
Patent number
US08524917B2

Reaction notes

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