Methanol → 1-(1-benzyloxycarbonylpiperidin-4-yl)-1H-indole-6-carboxylic acid

HRID 494911Notes

Reaction equation

HRID 494911 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]([O:28]C)=[O:27])[CH:24]=3)[CH:19]=[CH:18]2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.[OH-].[Na+].[Cl-].[NH4+]>O1CCCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]([OH:28])=[O:27])[CH:24]=3)[CH:19]=[CH:18]2)[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 57682829methyl 1-(1-benzyloxycarbonylpiperidin-4-yl)-1H-indole-6-carboxylate

Product 1

HCID 576829061-(1-benzyloxycarbonylpiperidin-4-yl)-1H-indole-6-carboxylic acidYield 87.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

90.0 g of methyl 1-(1-benzyloxycarbonylpiperidin-4-yl)-1H-indole-6-carboxylate was dissolved in a mixed solution consisting of 760 ml of methanol and 200 ml of tetrahydrofuran. Thereafter, 92 ml of a 5 N sodium hydroxide aqueous solution was added to the reaction solution, and the mixture was then heated to a temperature between 60° C. and 70° C. After completion of the reaction, the reaction solution was cooled, and 65.0 g of ammonium chloride was added thereto, followed by concentration under a reduced pressure. A 5% KHSO4 aqueous solution was added to the residue, so as to adjust pH to be 5 to 6, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated sodium chloride solution, and then dried over anhydrous magnesium sulfate. After removing the drying agent by filtration, the organic layer was concentrated under a reduced pressure. Thereafter, the residue was solidified, and then collected from a mixed solvent consisting of hexane and t-butylmethyl ether by filtration, so as to obtain 75.6 g of the subject compound.

Workup

  1. temperaturethe mixture was then heated to a temperature between 60° C. and 70° C
  2. customAfter completion of the reaction
  3. temperaturethe reaction solution was cooled
  4. concentrationfollowed by concentration under a reduced pressure
  5. additionA 5% KHSO4 aqueous solution was added to the residue
  6. extractionfollowed by extraction with ethyl acetate
  7. washThe organic layer was washed with water
  8. dry with materiala saturated sodium chloride solution, and then dried over anhydrous magnesium sulfate
  9. customAfter removing the drying agent
  10. filtrationby filtration
  11. concentrationthe organic layer was concentrated under a reduced pressure
  12. customcollected from a mixed solvent
  13. filtrationconsisting of hexane and t-butylmethyl ether by filtration

Sources & evidence

ORD record
ord-2d6025b98000440eb5e73734c5cfb996
Source dataset
uspto-grants-2009_05
Patent number
US07538123B2

Reaction notes

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