Sodium Hydroxide → 4-((1H-indol-3-yl)methyl)benzoic acid

HRID 1163094Notes

Reaction equation

HRID 1163094 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]2[CH:20]=[CH:19][C:14]([C:15]([O:17]C)=[O:16])=[CH:13][CH:12]=2)=[CH:2]1.[OH-].[Na+]>CO>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]2[CH:20]=[CH:19][C:14]([C:15]([OH:17])=[O:16])=[CH:13][CH:12]=2)=[CH:2]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 26367194methyl 4-((1H-indol-3-yl)methyl)benzoate

Product 1

HCID 684257424-((1H-indol-3-yl)methyl)benzoic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of methyl 4-((1H-indol-3-yl)methyl)benzoate (Tet. Lett. 44 (2003) 4589-4591) (0.50 g, 1.88-mmol) in methanol is treated with an aqueous solution of NaOH (4.15 mL, 1N, 4.15 mmol), heated to reflux temperature for 3 h and concentrated in vacuo. The resultant solid residue is dissolved in H2O and acidified with HCl. The resultant precipitate is removed by filtration and dried to yield 4-((1H-indol-3-yl)methyl)benzoic acid as a white solid, 0.468 g (99%). A microwave vial is charged with PS-Carbodiimide (0.275 g, 1.2 mmol/g, 0.33 mmol). To the vial is added a solution of 4-((1H-indol-3-yl)methyl)-benzoic acid (0.070 g, 0.28 mmol) in CH3CN, a solution of HOBT (0.045 g, 0.33 mmol) in CH3CN, a solution of (S)-1,3′-bipyrrolidine (0.065 g, 0.31 mmol) in CH3CN and 0.11 mL of triethylamine. The reaction mixture is irradiated in the Emry's Optimizer at 110° C. for 6 minutes and then concentrated under reduced pressure. The resultant residue is purified by flash chromatography to yield the title product as a white solid, 0.064 g, (68%), mp 141-153° C., identified by H1 NMR and mass spectral analyses. MS (ES) m/z 372.2.

Workup

  1. temperatureheated
  2. temperatureto reflux temperature for 3 h
  3. concentrationconcentrated in vacuo
  4. dissolutionThe resultant solid residue is dissolved in H2O
  5. customThe resultant precipitate is removed by filtration
  6. customdried

Sources & evidence

ORD record
ord-31099dd0a60e4d8d8aea6c63d7b86463
Source dataset
uspto-grants-2010_10
Patent number
US07820825B2

Reaction notes

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