Lithium hydroxide, monohydrate → 1-benzyl-3-phenyl-5-(1H-pyrrol-1-yl)-1H-indole-2-carboxylic acid

HRID 915340Notes

Reaction equation

HRID 915340 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([N:17]3[CH:21]=[CH:20][CH:19]=[CH:18]3)=[CH:14][CH:15]=2)[C:10]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:9]1[C:28]([O:30]CC)=[O:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[OH-].[Li+]>C1COCC1.CO.O>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([N:17]3[CH:18]=[CH:19][CH:20]=[CH:21]3)=[CH:14][CH:15]=2)[C:10]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:9]1[C:28]([OH:30])=[O:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 69341286ethyl 1-benzyl-3-phenyl-5-(1H-pyrrol-1-yl)-1H-indole-2-carboxylate

Product 1

HCID 114861671-benzyl-3-phenyl-5-(1H-pyrrol-1-yl)-1H-indole-2-carboxylic acidYield 94%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a stirred solution of ethyl 1-benzyl-3-phenyl-5-(1H-pyrrol-1-yl)-1H-indole-2-carboxylate (0.80 g, 1.9 mmol) in 20 mL of 2:1:1 THF/MeOH/water was added lithium hydroxide monohydrate (0.80 g, 19.0 mmol). The reaction was stirred at room temperature for 1 day. Most of the organic solvents was removed and the reaction mixture was made acidic (pH 6) with glacial acetic acid, and the solid was collected and purified by semi-preparative HPLC (Column: Phenomenex C18 Luna 21.6 mm×60 mm, 5 μM; Solvent A: Water (0.1% TFA buffer); Solvent B: Acetonitrile (0.1% TFA buffer); Solvent Gradient: Time 0:0% B; 10 min: 100% B; Hold 100% B 5 min. Flow Rate: 22.5 mL/min). The product was collected based on UV absorption and concentrated to give the title compound as a white solid (0.70 g, 94%): 1H NMR (DMSO-d6+CDC3) δ 5.88 (s, 2 H), 6.23 (t, J=2.1 Hz, 2 H), 7.02 (t, J=2.1 Hz, 2 H), 7.10-7.50 (m, 13 H); MS (ESI) m/z 393 (MH+); MS (ESI) m/z 391 ([M−H]−); HRMS calcd for C26H21N2O2: 393.1604; found (ESI+): 393.1590; Anal. calcd for C26H20N2O2: C, 79.57; H, 5.14; N, 7.14. Found: C, 79.25; H, 5.04; N, 7.12.

Workup

  1. customMost of the organic solvents was removed
  2. customthe solid was collected
  3. custompurified by semi-preparative HPLC (Column: Phenomenex C18 Luna 21.6 mm×60 mm, 5 μM; Solvent A: Water (0.1% TFA buffer); Solvent B: Acetonitrile (0.1% TFA buffer); Solvent Gradient: Time 0:0% B; 10 min: 100% B; Hold 100% B 5 min. Flow Rate: 22.5 mL/min)
  4. customThe product was collected
  5. custombased on UV absorption
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-fc30f6c1175845e8a3b94046948df3d3
Source dataset
uspto-grants-2007_09
Patent number
US07265148B2

Reaction notes

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