Potassium Hydroxide → 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indole-3-carboxylic acid

HRID 1512801Notes

Reaction equation

HRID 1512801 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[N:24]([CH3:26])[CH:23]=[C:22]4[CH:27]=[O:28])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[O-:29][Mn](=O)(=O)=O.[K+].[OH-].[K+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[N:24]([CH3:26])[CH:23]=[C:22]4[C:27]([OH:29])=[O:28])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 516875Potassium PermanganateHCID 591461277-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indole-3-carbaldehyde

Product 1

HCID 591460907-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indole-3-carboxylic acidYield 89.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
55 °C

Procedure

To a solution of 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indole-3-carbaldehyde (D61) (1.4 g) in THF (20 mL) was added KMnO4 (1.1 g) and aqueous KOH (10 mL). The reaction mixture was stirred at 55° C. overnight. After cooled to room temperature, the mixture was diluted with THF (30 mL), and filtered. The filtrate was concentrated and the aqueous suspension was acidified with aqueous HCl (2 M) to pH 5-6. The resulting white solid was collected, washed with water, dried in vacuo to give the crude compound, which was purified by column chromatography (10% ethyl acetate in hexane) to afford 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indole-3-carboxylic acid (D95) as a white solid (1.3 g). δH (DMSO-d6, 400 MHz): 1.36 (6H, d), 3.74 (3H, s), 4.88 (1H, m), 7.35 (1H, dd), 7.45 (1H, d), 7.53 (1H, dd), 8.12 (1H, d), 8.14 (1H, d), 8.20 (1H, d), 8.32 (1H, dd), 12.15 (1H, s). MS (ES): C21H18ClN3O4 requires 411. found 412.1 (M+H+).

Workup

  1. temperatureAfter cooled to room temperature
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. customThe resulting white solid was collected
  5. washwashed with water
  6. customdried in vacuo
  7. customto give the crude compound, which
  8. customwas purified by column chromatography (10% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-4d015fc173af4842a024b3842924d05d
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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