Sodium Hydroxide → 4-((1-(Tert-butoxycarbonyl)piperidin-4-YL)oxy)-2-methoxybenzoic acid

HRID 1292035Notes

Reaction equation

HRID 1292035 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21]C)=[O:20])=[C:17]([O:25][CH3:26])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([O:14][C:15]2[CH:24]=[CH:23][C:18]([C:19]([OH:21])=[O:20])=[C:17]([O:25][CH3:26])[CH:16]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 10570851Tert-butyl 4-(3-methoxy-4-(methoxycarbonyl)phenoxy)piperidine-1-carboxylate

Product 1

HCID 105458744-((1-(Tert-butoxycarbonyl)piperidin-4-YL)oxy)-2-methoxybenzoic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

Methyl 4-(N-t-butoxycarbonyl-4-piperidinyloxy)-2-methoxybenzoate (35 g, 96 mmol) from Step 5 above was dissolved in MeOH (250 mL) and to the solution was added 2 N NaOH (100 ML, 200 mmol). The stirred mixture was warmed to 70° C. for 3 h. The solution was cooled to ambient temperature, concentrated under reduced pressure, cooled to 0° C. and 0.5M aqueous citric acid solution (300 mL) was added. To the suspension was added EtOAc (500 mL) and water (300 mL). The EtOAc layer was separated and the aqueous phase was washed with EtOAc (200 mL). The combined EtOAc layers were washed with brine (250 mL), dried (MgSO4), filtered, and the solvent was removed under reduced pressure to give 4-(N-t-butoxycarbonyl-4-piperidinyloxy)-2-methoxybenzoic acid as a foam that solidified on standing in vacuo (HPLC (method A) retention time= 8.46 min).

Workup

  1. temperatureThe solution was cooled to ambient temperature
  2. concentrationconcentrated under reduced pressure
  3. temperaturecooled to 0° C.
  4. addition0.5M aqueous citric acid solution (300 mL) was added
  5. additionTo the suspension was added EtOAc (500 mL) and water (300 mL)
  6. customThe EtOAc layer was separated
  7. washthe aqueous phase was washed with EtOAc (200 mL)
  8. washThe combined EtOAc layers were washed with brine (250 mL)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-63a764325c2d43669d97a80387ab8545
Source dataset
uspto-grants-1998_05
Patent number
US05756497

Reaction notes

Loading…