Water → methyl 1-(1-benzyloxycarbonylpiperidin-4-yl)-1H-indole-6-carboxylate

HRID 494910Notes

Reaction equation

HRID 494910 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH2:12][CH:13](OC)OC)[C:5]([O:7][CH3:8])=[O:6].O=[C:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[O:26])[CH2:21][CH2:20]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>C(O)(=O)C>[CH2:28]([O:27][C:25]([N:22]1[CH2:23][CH2:24][CH:19]([N:1]2[C:2]3[C:11](=[CH:10][CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[CH:3]=3)[CH:12]=[CH:13]2)[CH2:20][CH2:21]1)=[O:26])[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

6

Reactant 4

HCID 962WaterHCID 643496Benzyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 11053739Methyl 3-amino-4-(2,2-dimethoxyethyl)benzoate

Product 1

HCID 57682829methyl 1-(1-benzyloxycarbonylpiperidin-4-yl)-1H-indole-6-carboxylateYield 88.9%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

44.3 g of methyl 3-amino-4-(2,2-dimethoxyethyl)benzoate synthesized according to the publication (Tetrahedron Letters, Vol. 37, No. 34, pp. 6045-6048) and 64.9 g of benzyl 4-oxo-1-piperidinecarboxylate were dissolved in 485 ml of acetic acid, followed by stirring at room temperature. Approximately 20 minutes later, 58.9 g of sodium triacetoxyborohydride was added to the reaction solution. Then, the reaction solution was further stirred for 2 hours. Thereafter, 485 ml of water was added to the reaction solution, and the obtained mixture was heated to a temperature between 100° C. and 115° C. Approximately 3 hours later, the reaction solution was cooled, and then concentrated under a reduced pressure. Thereafter, water and ethyl acetate were added thereto, so as to separate an organic layer. The obtained organic layer was washed with a saturated sodium bicarbonate aqueous solution and a saturated sodium chloride solution, and dried over anhydrous magnesium sulfate. After removing the drying agent by filtration, the organic layer was concentrated under a reduced pressure, and the residue was then purified by NH silica gel column chromatography (hexane/ethyl acetate). The obtained solid was suspended in a mixed solvent consisting of hexane and t-butylmethyl ether, followed by filtration, so as to obtain 64.6 g of the subject compound.

Workup

  1. stirringThen, the reaction solution was further stirred for 2 hours
  2. temperaturethe obtained mixture was heated to a temperature between 100° C. and 115° C
  3. temperatureApproximately 3 hours later, the reaction solution was cooled
  4. concentrationconcentrated under a reduced pressure
  5. additionThereafter, water and ethyl acetate were added
  6. customso as to separate an organic layer
  7. washThe obtained organic layer was washed with a saturated sodium bicarbonate aqueous solution
  8. dry with materiala saturated sodium chloride solution, and 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. customthe residue was then purified by NH silica gel column chromatography (hexane/ethyl acetate)
  13. filtrationfollowed by filtration

Sources & evidence

ORD record
ord-a969e02125f649b4ab785d38244d7c3e
Source dataset
uspto-grants-2009_05
Patent number
US07538123B2

Reaction notes

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