Sodium Hydroxide → 3-[5-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]propanoic acid

HRID 2189807Notes

Reaction equation

HRID 2189807 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]=[C:19]4[C:23](=[CH:24][CH:25]=3)[N:22]([CH2:26][CH2:27][C:28]([O:30]CC)=[O:29])[N:21]=[CH:20]4)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[C:19]4[C:23](=[CH:24][CH:25]=3)[N:22]([CH2:26][CH2:27][C:28]([OH:30])=[O:29])[N:21]=[CH:20]4)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59316704Ethyl 3-[5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]propanoate

Product 1

HCID 250223293-[5-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]propanoic acidYield 5.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Ethyl 3-[5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]propanoate (D5) (240 mg) was dissolved in MeOH (5 ml), treated with 2 M aqueous NaOH (5 ml) and stirred at RT overnight and vacuumed to remove the MeOH. The reaction mixture was then diluted with 1M aqueous NaOH, washed with EtOAc (×2) and acidified to pH=3. This solution was extracted with EtOAc (×3) and the combined extracts washed with brine and evaporated to give the crude product. This was purified using the MDAP system to give the title compound (13 mg) as a white solid. δH (CDCl3, 400 MHz): 1.44 (6H, d), 3.03 (2H, t), 4.68-4.75 (3H, m), 7.05 (1H, d), 7.60 (1H, d), 8.06 (1H, d), 8.11 (1H, s), 8.15 (1H, d), 8.24 (1H, s), 8.56 (1H, s). MS (ES): C21H1935ClN4O4 requires 426; found 427 (MH+).

Workup

  1. customto remove the MeOH
  2. additionThe reaction mixture was then diluted with 1M aqueous NaOH
  3. washwashed with EtOAc (×2)
  4. extractionThis solution was extracted with EtOAc (×3)
  5. washthe combined extracts washed with brine
  6. customevaporated
  7. customto give the crude product
  8. customThis was purified

Sources & evidence

ORD record
ord-d96b406fbbe94b8d9c13f1c7ef35880f
Source dataset
uspto-grants-2012_12
Patent number
US08324254B2

Reaction notes

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