Hydrochloric Acid → 4-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]butanoic acid

HRID 1512894Notes

Reaction equation

HRID 1512894 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[CH2:27][CH2:28][CH2:29][C:30]([O:32]CC)=[O:31])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+].Cl>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[CH2:27][CH2:28][CH2:29][C:30]([OH:32])=[O:31])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 59146117HCID 59146117, compound

Product 1

HCID 445480624-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]butanoic acidYield 17.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of ethyl 4-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]butanoate (D57) (120 mg) in THF (5 mL) was added aqueous NaOH (2M, 2 mL). The reaction was stirred at 60° C. overnight. The mixture was acidified with aqueous HCl (2M) to pH 5-6, partitioned between ethyl acetate (20 mL) and water (20 mL). The organic phase was separated and dried over anhydrous sodium sulphate. After removing the solvent, the crude product was purified by TLC separation to afford 4-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]butanoic acid (E35) (20 mg). δH (DMSO-d6, 400 MHz): 1.36 (6H, d), 1.89 (2H, m), 2.29 (2H, t), 2.74 (2H, t), 3.63 (3H, s), 4.88 (1H, m), 7.17 (2H, m), 7.44 (2H, m), 7.77 (1H, d), 8.12 (1H, dd), 8.19 (1H, d), 11.98 (1H, br s). MS (ES): C24H24ClN3O4 requires 453; found 454.2 (M+H+).

Workup

  1. custompartitioned between ethyl acetate (20 mL) and water (20 mL)
  2. customThe organic phase was separated
  3. dry with materialdried over anhydrous sodium sulphate
  4. customAfter removing the solvent
  5. customthe crude product was purified by TLC separation

Sources & evidence

ORD record
ord-f13fd4ead04241bc89777b5fdf068eda
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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