1,1'-Carbonyldiimidazole → Benzyl 4-(6-carbamoyl-1H-indol-1-yl)piperidine-1-carboxylate

HRID 494912Notes

Reaction equation

HRID 494912 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)=O)[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.C(N1C=CN=C1)(N1C=CN=C1)=O.[OH2:41].[NH4+:42]>O1CCCC1>[C:26]([C:23]1[CH:24]=[C:25]2[C:20]([CH:19]=[CH:18][N:17]2[CH:14]2[CH2:13][CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[O:10])[CH2:16][CH2:15]2)=[CH:21][CH:22]=1)(=[O:41])[NH2:42]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 22024077Azanium;hydrateHCID 576829061-(1-benzyloxycarbonylpiperidin-4-yl)-1H-indole-6-carboxylic acid

Product 1

HCID 57682819Benzyl 4-(6-carbamoyl-1H-indol-1-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

75.0 g of 1-(1-benzyloxycarbonylpiperidin-4-yl)-1H-indole-6-carboxylic acid was dissolved in 620 ml of tetrahydrofuran. Thereafter, 38.6 g of 1,1′-carbonylbis-1H-imidazole was added thereto. The reaction solution was stirred at room temperature for 1.5 hours, and 134 ml of a 28% ammonium water was then added thereto. After completion of the reaction, the reaction solution was concentrated under a reduced pressure, and then extracted with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride solution and a saturated ammonium chloride aqueous solution. Tetrahydrofuran was added to the separated organic layer, and a partially solidified subject compound was dissolved therein, followed by drying over anhydrous magnesium sulfate. After removing the drying agent by filtration, the organic layer was concentrated under a reduced pressure. The solidified subject compound was collected by filtration. The thus collected subject compound was suspended in tetrahydrofuran, and the mixture was heated, followed by filtration. The thus collected subject compound was then suspended in a mixed solvent consisting of tetrahydrofuran and methanol, and the obtained mixture was heated, followed by filtration. The generated filtrates were gathered and concentrated, and thus, the subject compound was obtained in the same above manner. The total amount of the subject compounds was 64.8 g.

Workup

  1. customAfter completion of the reaction
  2. concentrationthe reaction solution was concentrated under a reduced pressure
  3. extractionextracted with ethyl acetate
  4. washThe obtained organic layer was washed with a saturated sodium chloride solution
  5. additionTetrahydrofuran was added to the separated organic layer
  6. dissolutiona partially solidified subject compound was dissolved
  7. dry with materialby drying over anhydrous magnesium sulfate
  8. customAfter removing the drying agent
  9. filtrationby filtration
  10. concentrationthe organic layer was concentrated under a reduced pressure
  11. filtrationThe solidified subject compound was collected by filtration
  12. customThe thus collected
  13. temperaturethe mixture was heated
  14. filtrationfollowed by filtration
  15. customThe thus collected
  16. temperaturethe obtained mixture was heated
  17. filtrationfollowed by filtration
  18. concentrationconcentrated
  19. customthus, the subject compound was obtained in the same above manner

Sources & evidence

ORD record
ord-dc5d12b29833485ebf32de5ea7dbc18c
Source dataset
uspto-grants-2009_05
Patent number
US07538123B2

Reaction notes

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