Sodium Hydroxide → 3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1-methyl-1H-indol-3-yl]propanoic acid

HRID 1512954Notes

Reaction equation

HRID 1512954 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[C:18]([F:34])=[CH:19][CH:20]=[C:21]4[C:25]=3[N:24]([CH3:26])[CH:23]=[C:22]4[CH2:27][CH2:28][C:29]([O:31]CC)=[O:30])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+]>C(O)(C)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[C:18]([F:34])=[CH:19][CH:20]=[C:21]4[C:25]=3[N:24]([CH3:26])[CH:23]=[C:22]4[CH2:27][CH2:28][C:29]([OH:31])=[O:30])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 59146081HCID 59146081, compound

Product 1

HCID 445471753-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1-methyl-1H-indol-3-yl]propanoic acidYield 43.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of ethyl 3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1-methyl-1H-indol-3-yl]propanoate (D147) (330 mg) in isopropanol (7 mL) and water (7 mL) was added NaOH (6.79 mL, 0.5 M aqueous solution) at room temperature. The reaction suspension was stirred at 90° C. for 2 hours, and the solution turned clear. Isopropanol was removed in vacuo and water (8 mL) was added to the residue. The aqueous solution was acidified to pH=1 and extracted with ethyl acetate (3×10 mL). The combined organic phase was dried over sodium sulphate. The organic solution was concentrated and the residue was purified by MDAP to afford 3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1-methyl-1H-indol-3-yl]propanoic acid (E104) (136 mg) as a white solid. δH (DMSO-d6, 400 MHz): 1.29 (6H, s), 2.53 (2H, t), 2.87 (2H, t), 3.29 (3H, s), 4.83 (1H, m), 7.02 (1H, m), 7.10 (1H, s), 7.39 (1H, d), 7.75 (1H, m), 8.07 (1H, dd), 8.14 (1H, d), 12.07 (1H, s). MS (ES): C23H21ClFN3O4 requires 457; found 458.2 (M+H+).

Workup

  1. customIsopropanol was removed in vacuo and water (8 mL)
  2. additionwas added to the residue
  3. extractionextracted with ethyl acetate (3×10 mL)
  4. dry with materialThe combined organic phase was dried over sodium sulphate
  5. concentrationThe organic solution was concentrated
  6. customthe residue was purified by MDAP

Sources & evidence

ORD record
ord-34a4111816064f3dafe8f079faf9f85f
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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