Sodium Hydroxide → Sodium 3-(4-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)propanoate

HRID 423377Notes

Reaction equation

HRID 423377 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:15][N:14]=[C:13]([C:16]3[CH:24]=[CH:23][CH:22]=[C:21]4[C:17]=3[CH:18]=[CH:19][N:20]4[CH2:25][CH2:26][C:27]([O:29]CC)=[O:28])[N:12]=2)=[CH:7][C:6]=1[C:32]([F:35])([F:34])[F:33])[CH3:3].[OH-].[Na+:37]>C(O)C>[CH3:3][CH:2]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:15][N:14]=[C:13]([C:16]3[CH:24]=[CH:23][CH:22]=[C:21]4[C:17]=3[CH:18]=[CH:19][N:20]4[CH2:25][CH2:26][C:27]([O-:29])=[O:28])[N:12]=2)=[CH:7][C:6]=1[C:32]([F:35])([F:34])[F:33])[CH3:1].[Na+:37]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59318349Ethyl 3-(4-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)propanoate

Product 1

HCID 66677381Sodium 3-(4-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)propanoateYield 69.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of ethyl 3-(4-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)propanoate (D72) (81 mg, 0.17 mmol) in ethanol (8 mL) was added aqueous sodium hydroxide (2M, 0.8 mL, 1.6 mmol) and the reaction heated to 50° C. to dissolve the reagents before heating at 40° C. for 1 h. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (20 mL) and water (20 mL) and acidified with aqueous hydrochloric acid (2M). The aqueous phase was extracted with further ethyl acetate (2×20 mL) and the combined organic extracts dried (phase separator) and concentrated in vacuo. The solid was then dissolved in acetonitrile and water with addition of an equimolar amount of sodium hydroxide (2M) before the solution was freeze-dried to give the title compound (57 mg). δH (d6-DMSO, 400 MHz): 8.44 (1H, dd), 8.35 (1H, d), 7.93 (1H, dd), 7.74 (1H, d), 7.65-7.54 (2H, m), 7.31 (1H, app. t), 7.00 (1H, dd) 4.99 (1H, septet), 4.38 (2H, t), 2.34 (2H, t), 1.36 (6H, d). MS (ES): C23H20F3N3O4 requires 459; found 460 (MH+).

Workup

  1. dissolutionto dissolve the reagents
  2. temperaturebefore heating at 40° C. for 1 h
  3. customThe solvent was removed in vacuo
  4. customthe residue partitioned between ethyl acetate (20 mL) and water (20 mL)
  5. extractionThe aqueous phase was extracted with further ethyl acetate (2×20 mL)
  6. customthe combined organic extracts dried (phase separator)
  7. concentrationconcentrated in vacuo
  8. dissolutionThe solid was then dissolved in acetonitrile
  9. additionwater with addition of an equimolar amount of sodium hydroxide (2M) before the solution
  10. customwas freeze-dried

Sources & evidence

ORD record
ord-8da687783cdd4684a3b20c9cfd05b9cd
Source dataset
uspto-grants-2012_01
Patent number
US08101775B2

Reaction notes

Loading…