Methanol → 6-cyano-3-methyl-1-(1-methylethyl)-1H-indole-4-carboxylic acid

HRID 593902Notes

Reaction equation

HRID 593902 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:16]([O:18]C)=[O:17])[C:6]2[C:7]([CH3:15])=[CH:8][N:9]([CH:12]([CH3:14])[CH3:13])[C:10]=2[CH:11]=1)#[N:2].CO.[OH-].[Na+]>C1COCC1>[C:1]([C:3]1[CH:4]=[C:5]([C:16]([OH:18])=[O:17])[C:6]2[C:7]([CH3:15])=[CH:8][N:9]([CH:12]([CH3:14])[CH3:13])[C:10]=2[CH:11]=1)#[N:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 67467281methyl 6-cyano-1-isopropyl-3-methyl-1H-indole-4-carboxylate

Product 1

HCID 674680896-cyano-3-methyl-1-(1-methylethyl)-1H-indole-4-carboxylic acidYield 64.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 50 ml round bottom was added methyl 6-cyano-3-methyl-1-(1-methylethyl)-1H-indole-4-carboxylate (230 mg, 0.897 mmol), followed by methanol (1 mL) and THF (1 mL). To the solution was added 3M NaOH (0.449 mL, 2.69 mmol). The reaction stirred at rt for 20 h. The reaction was evaporated and treated with acidic water to pH 5. A brown solid crashed out and was collected by filtration. The solid was an impurity. The pH of the liquid was adjusted to 3 and the liquid was evaporated leaving a residue. Trituration of the residue with water, followed by filtration yielded 6-cyano-3-methyl-1-(1-methylethyl)-1H-indole-4-carboxylic acid (155 mg, 0.576 mmol, 64.2% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.16 (br. s., 1H) 8.33 (s, 1H) 7.78 (s, 1H) 7.66 (s, 1H) 4.81-4.98 (m, 1H) 2.33 (s, 4H) 1.45 (d, J=6.57 Hz, 6H). MS(ES) [M+H]+ 243.3.

Workup

  1. customThe reaction was evaporated
  2. additiontreated with acidic water to pH 5
  3. filtrationwas collected by filtration
  4. customthe liquid was evaporated
  5. customleaving a residue
  6. filtrationTrituration of the residue with water, followed by filtration

Sources & evidence

ORD record
ord-f93c731a88cc4e44b9190ace3bfd09f6
Source dataset
uspto-grants-2016_01
Patent number
US09242962B2

Reaction notes

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