Sodium Hydroxide → 5-Nitroindole-2-carboxylic acid

HRID 2054711Notes

Reaction equation

HRID 2054711 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8]([C:13]([O:15]CC)=[O:14])=[CH:7]2)([O-:3])=[O:2].[OH-].[Na+]>C1COCC1.CO.O>[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8]([C:13]([OH:15])=[O:14])=[CH:7]2)([O-:3])=[O:2]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 280312Ethyl 5-nitro-1H-indole-2-carboxylate

Product 1

HCID 3512915-Nitroindole-2-carboxylic acidYield 96%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl-5-nitroindole-2-carboxylate (8) (25.0 g, 106.8 mmol), in 500 mL of THF-methanol (1:1, v/v) at room temperature, was added a solution of NaOH (40 g, 1.0 mmol) in 300 mL of water. The resulting deep red-brown solution was stirred for 3 h, then quenched by acidification to pH 1 with dilute HCl. The precipitated product was collected by vacuum filtration, and the remaining dissolved product was extracted with THF/ethyl acetate (1:2, v/v, 2×400 mL). The precipitate was dissolved in THF and this solution was combined with the organic layers from the extractions, supra. Drying over magnesium sulfate, filtration, concentration in vacuo, and crystallization of the residue from THF/ethyl acetate/hexane afforded 21.1 g (96% yield) of 5-nitroindole-2-carboxylic acid (9). 1H NMR (DMSO), 11.50 (s, 1H), 7.20 (d, 1H, J=8.4 Hz), 6.85 (s, 1H), 6.70 (m, 2H).

Workup

  1. customquenched by acidification to pH 1 with dilute HCl
  2. filtrationThe precipitated product was collected by vacuum filtration
  3. dissolutionthe remaining dissolved product
  4. extractionwas extracted with THF/ethyl acetate (1:2, v/v, 2×400 mL)
  5. dissolutionThe precipitate was dissolved in THF
  6. extractionthis solution was combined with the organic layers from the extractions, supra
  7. dry with materialDrying over magnesium sulfate, filtration, concentration in vacuo, and crystallization of the residue from THF/ethyl acetate/hexane

Sources & evidence

ORD record
ord-2e89664af2c341979b9ddcd7cce34e88
Source dataset
uspto-grants-2008_02
Patent number
US07329760B2

Reaction notes

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