Indole → tert-Butyl 4-(1H-indol-3-yl)-3,6-dihydropyridine-1(2H)-carboxylate

HRID 1683934Notes

Reaction equation

HRID 1683934 reaction equation
[Na].[NH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3]1.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]>CO>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][C:21]([C:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[NH:2][CH:3]=2)=[CH:20][CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

5

Reactant 3

HCID 798Indole2×HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5360545Sodium

Product 1

HCID 16227686tert-Butyl 4-(1H-indol-3-yl)-3,6-dihydropyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

To a stirred solution of sodium (2.51 g, 105 mmol, 7 eq) in absolute methanol (50 mL) was added the indole (15.0 mmol) and N-t-butoxycarbonyl-4-piperidone (8.96 g, 45.0 mmol 3.0 eq). The resulting reaction solution was heated at reflux (65° C.) under nitrogen for 3-24 hours, depending on the indole used. The resulting reaction solution was evaporated under reduced pressure, and the residue was partitioned between a saturated solution of sodium hydrogen carbonate (50 mL) and ethyl acetate (50 mL). The organic layer was removed, and the aqueous layer was extracted with ethyl acetate (2×50 mL). The organic extracts were combined, dried (MgSO4), and evaporated under reduced pressure. The residue was purified either by trituration in diethyl ether or by column chromatography to afford the desired 3-(N-t-butoxycarbonyl-1,2,5,6-tetrahydropyrid-4-yl)-1H-indole.

Workup

  1. customThe resulting reaction solution
  2. temperaturewas heated
  3. customThe resulting reaction solution
  4. customwas evaporated under reduced pressure
  5. customthe residue was partitioned between a saturated solution of sodium hydrogen carbonate (50 mL) and ethyl acetate (50 mL)
  6. customThe organic layer was removed
  7. extractionthe aqueous layer was extracted with ethyl acetate (2×50 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated under reduced pressure
  10. customThe residue was purified either by trituration in diethyl ether or by column chromatography

Sources & evidence

ORD record
ord-b74b9d0869cb4105a1a260b90d17f5f3
Source dataset
uspto-grants-1997_06
Patent number
US05639752

Reaction notes

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