Sodium Hydroxide → HCID 66677224, compound

HRID 423376Notes

Reaction equation

HRID 423376 reaction equation
[CH:1]1([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[O:17][N:16]=[C:15]([C:18]4[CH:26]=[CH:25][CH:24]=[C:23]5[C:19]=4[CH:20]=[CH:21][N:22]5[CH2:27][CH2:28][C:29]([O:31]CC)=[O:30])[N:14]=3)=[CH:9][C:8]=2[C:34]([F:37])([F:36])[F:35])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+:39]>C(O)C>[CH:1]1([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[O:17][N:16]=[C:15]([C:18]4[CH:26]=[CH:25][CH:24]=[C:23]5[C:19]=4[CH:20]=[CH:21][N:22]5[CH2:27][CH2:28][C:29]([O-:31])=[O:30])[N:14]=3)=[CH:9][C:8]=2[C:34]([F:35])([F:36])[F:37])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1.[Na+:39]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59318369HCID 59318369, compound

Product 1

HCID 66677224HCID 66677224, compoundYield 67.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
40 °C

Procedure

Ethyl 3-(4-{5-[4-cyclohexyl-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)propanoate (D69) (63 mg, 0.123 mmol) was dissolved in ethanol (8 ml) and sodium hydroxide (2M, 0.5 ml, 1.000 mmol) was added. The reaction was heated at 40° C. for 18 h. LCMS showed complete conversion to product. The reaction mixture was concentrated in vacuo and the white solid filtered off and washed with water. On filtration, much compound redissolved and passed through, so solid and filtrate were combined and separated between dichloromethane (10 mL) and 2M HCl (3 mL). The aqueous phase was extracted with further dichloromethane (10 mL). The organic phases were isolated by phase separator, combined and the solvent removed in vacuo. The solid was then dissolved in acetonitrile and water with addition of an equimolar amount of sodium hydroxide (2M, 53 μL) before the solution was freeze-dried to give the title compound (42 mg) as a white solid. δH (methanol-d4, 400 MHz): 8.48 (1H, d), 8.43 (1H, dd), 7.98 (1H, dd), 7.86 (1H, d), 7.73 (1H, d), 7.46 (1H, d), 7.32 (1H, app. t), 7.15 (1H, dd), 4.52 (2H, t), 3.04 (1H, t), 2.69 (2H, t), 2.0-1.8 (5H, m), 1.63 (2H, dd), 1.53-1.37 (3H, m). MS (ES) C26H24F3N3O3 requires 483; found 482 (M−H+).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. filtrationthe white solid filtered off
  3. washwashed with water
  4. filtrationOn filtration, much compound
  5. dissolutionredissolved
  6. customseparated between dichloromethane (10 mL) and 2M HCl (3 mL)
  7. extractionThe aqueous phase was extracted with further dichloromethane (10 mL)
  8. customThe organic phases were isolated by phase separator
  9. customthe solvent removed in vacuo
  10. dissolutionThe solid was then dissolved in acetonitrile
  11. additionwater with addition of an equimolar amount of sodium hydroxide (2M, 53 μL) before the solution
  12. customwas freeze-dried

Sources & evidence

ORD record
ord-06348d362c034899866cf11db626ea00
Source dataset
uspto-grants-2012_01
Patent number
US08101775B2

Reaction notes

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