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

HRID 1512800Notes

Reaction equation

HRID 1512800 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[NH:24][CH:23]=[C:22]4[CH:26]=[O:27])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[O-:28][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[NH:24][CH:23]=[C:22]4[C:26]([OH:28])=[O:27])[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 591461517-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole-3-carbaldehyde

Product 1

HCID 591460637-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole-3-carboxylic acid

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)-1H-indole-3-carbaldehyde (D71) (1.1 g) in THF (20 mL) was added KMnO4 (0.9 g) and aqueous KOH (10 mL). The reaction was stirred at 55° C. overnight. After cooled to room temperature, the mixture was diluted with THF (20 mL) and filtered. The filtrate was concentrated and the aqueous suspension was acidified with aqueous HCl (2 M) to pH 5-6. The resulting solid was collected by filtration, washed with water, dried in vacuo to give the crude compound, which was purified by column chromatography (20% ethyl acetate in hexane) to afford 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole-3-carboxylic acid as a white solid (D94) (1.0 g). δH (DMSO-d6, 400 MHz): 1.36 (6H, d), 4.90 (1H, m), 7.38 (1H, t), 7.46 (1H, d), 8.02 (2H, m), 8.22 (1H, dd), 8.30 (1H, dd), 8.41 (1H, d), 11.66 (1H, br s). MS (ES): C20H16ClN3O4 requires 397; found 398.1 (M+H+).

Workup

  1. temperatureAfter cooled to room temperature
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. filtrationThe resulting solid was collected by filtration
  5. washwashed with water
  6. customdried in vacuo
  7. customto give the crude compound, which
  8. customwas purified by column chromatography (20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-5a3f617141754b31877f84c801181833
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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