Methanol → 3-(5-{5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)propanoic acid

HRID 423361Notes

Reaction equation

HRID 423361 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:22]=[C:23]5[C:27](=[CH:28][CH:29]=4)[N:26]([CH2:30][CH2:31][C:32]([O:34]CC)=[O:33])[CH:25]=[CH:24]5)[N:17]=3)[S:10][C:11]=2[C:12]([F:15])([F:14])[F:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CO>[OH-].[Na+].C(Cl)(Cl)Cl>[C:1]1([C:7]2[CH:8]=[C:9]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:22]=[C:23]5[C:27](=[CH:28][CH:29]=4)[N:26]([CH2:30][CH2:31][C:32]([OH:34])=[O:33])[CH:25]=[CH:24]5)[N:17]=3)[S:10][C:11]=2[C:12]([F:14])([F:15])[F:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 2

HCID 887MethanolHCID 59318376Ethyl 3-(5-{5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)propanoate

Product 1

HCID 248247243-(5-{5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)propanoic acidYield 8.4%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
50 °C

Procedure

D3 (38 mg) was dissolved in 2M aqueous NaOH (0.5 ml) and MeOH (0.5 ml) then stirred at RT overnight. LCMS analysis showed 41% product so the reaction mixture was heated to 50° C. and stirred over the weekend. LCMS showed the reaction to be complete. The reaction mixture was evaporated then partitioned between H2O and DCM. The organic layer was extracted with H2O. The combined aqueous extracts were acidified to pH=1 and extracted with DCM. These DCM extracts were dried over MgSO4, filtered and evaporated to give the crude product MF105672-149A1 (30 mg). The crude product was purified on a silica cartridge (12+S), eluting with a 0 to 10% mixture of MeOH in DCM to give the purified product. This was dissolved in CHCl3 and evaporated to give the title compound (3 mg) as a white solid. δH (CDCl3, 400 MHz): 2.92 (2H, t), 4.50 (2H, t), 6.51 (1H, d), 7.24 (1H, d), 7.40-7.53 (6H, m), 7.90 (1H, s), 8.00 (1H, d), 8.45 (1H, s). MS (ES+): C24H16F3N3O3S requires 483; found 484 (MH+).

Workup

  1. customthe reaction
  2. customThe reaction mixture was evaporated
  3. customthen partitioned between H2O and DCM
  4. extractionThe organic layer was extracted with H2O
  5. extractionextracted with DCM
  6. dry with materialThese DCM extracts were dried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto give the crude product
  10. customThe crude product was purified on a silica cartridge (12+S)
  11. washeluting with a 0 to 10% mixture of MeOH in DCM
  12. customto give the purified product
  13. customevaporated

Sources & evidence

ORD record
ord-3e3f2eb71fe1474b80a9ffa04698e0f7
Source dataset
uspto-grants-2012_01
Patent number
US08101775B2

Reaction notes

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