Sodium Hydroxide → 2-(5-((1-(Tert-butoxycarbonyl)piperidin-4-yl)oxy)-2-hydroxybenzamido)-4-phenylbenzoic acid

HRID 454624Notes

Reaction equation

HRID 454624 reaction equation
[OH-].[Na+].C([O:10][C:11]1[CH:47]=[CH:46][C:45]([O:48][CH:49]2[CH2:54][CH2:53][N:52]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:51][CH2:50]2)=[CH:44][C:12]=1[C:13]([NH:15][C:16]1[CH:37]=[C:36]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:35]=[CH:34][C:17]=1[C:18]([O:20]C1CCN(C(OC(C)(C)C)=O)CC1)=[O:19])=[O:14])C1C=CC=CC=1>CO.O1CCOCC1>[C:58]([O:57][C:55]([N:52]1[CH2:53][CH2:54][CH:49]([O:48][C:45]2[CH:46]=[CH:47][C:11]([OH:10])=[C:12]([CH:44]=2)[C:13]([NH:15][C:16]2[CH:37]=[C:36]([C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)[CH:35]=[CH:34][C:17]=2[C:18]([OH:20])=[O:19])=[O:14])[CH2:50][CH2:51]1)=[O:56])([CH3:61])([CH3:59])[CH3:60]

Participants

5

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 66990014Tert-butyl 4-(2-(2-(benzyloxy)-5-((1-(tert-butoxycarbonyl)piperidin-4-yl)oxy)benzamido)-4-phenylbenzoyloxy)piperidine-1-carboxylate

Product 1

HCID 585087442-(5-((1-(Tert-butoxycarbonyl)piperidin-4-yl)oxy)-2-hydroxybenzamido)-4-phenylbenzoic acidYield 50.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A 2 mol/L aqueous solution of sodium hydroxide (0.13 mL) was added to a solution mixture of the obtained tert-butyl 4-(2-(2-(benzyloxy)-5-((1-(tert-butoxycarbonyl)piperidin-4-yl)oxy)benzamido)-4-phenylbenzoyloxy)piperidine-1-carboxylate (0.072 g) in methanol (1 mL) and dioxane (1 mL), followed by stirring at room temperature for 1 hour. A 2 mol/L aqueous solution of sodium hydroxide (0.089 mL) was added to the reaction mixture, followed by heating to reflux for 20 minutes. After cooling the reaction mixture to room temperature, the solvent was evaporated under reduced pressure, and water was added to the obtained residue. After adjusting the pH to 3.5 with a 10% aqueous solution of citric acid, ethyl acetate was added thereto. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. To a solution mixture of the obtained residue, 10% palladium-carbon (0.039 g) in methanol (1.5 mL) and ethyl acetate (1.5 mL) was added, followed by stirring under a hydrogen atmosphere at room temperature for 2 hours. Ethyl acetate was added to the reaction mixture, and the insoluble substance was removed by filtration. The solvent was evaporated under reduced pressure, and diisopropyl ether was added to the obtained residue. The solid substance was collected by filtration to obtain 0.024 g of 2-(5-((1-(tert-butoxycarbonyl)piperidin-4-yl)oxy)-2-hydroxybenzamido)-4-phenylbenzoic acid as a light yellow solid.

Workup

  1. temperatureby heating
  2. temperatureto reflux for 20 minutes
  3. temperatureAfter cooling the reaction mixture to room temperature
  4. customthe solvent was evaporated under reduced pressure, and water
  5. additionwas added to the obtained residue
  6. additionwas added
  7. customThe organic layer was separated
  8. washwashed with a saturated aqueous solution of sodium chloride
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. additionTo a solution mixture of the obtained residue, 10% palladium-carbon (0.039 g) in methanol (1.5 mL) and ethyl acetate (1.5 mL)
  12. additionwas added
  13. stirringby stirring under a hydrogen atmosphere at room temperature for 2 hours
  14. additionEthyl acetate was added to the reaction mixture
  15. customthe insoluble substance was removed by filtration
  16. customThe solvent was evaporated under reduced pressure, and diisopropyl ether
  17. additionwas added to the obtained residue
  18. filtrationThe solid substance was collected by filtration

Sources & evidence

ORD record
ord-2f5ae445ce8c41a99b6c15de718f5555
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

Loading…