Water → HCID 58575213, compound

HRID 1189476Notes

Reaction equation

HRID 1189476 reaction equation
[CH2:1]([N:8]1[CH2:13][CH:12]=[C:11]([N:14]2CCCC2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br.Br[CH2:21][C:22]([C:24]1[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=1)=O.O>C1C=CC=CC=1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]2[NH:14][C:22]([C:24]3[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=3)=[CH:21][C:10]=2[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 962WaterHCID 27762394-(Bromoacetyl)pyridine hydrobromideHCID 117468121-Benzyl-4-(1-pyrrolidinyl)-1,2,3,6-tetrahydropyridine

Product 1

HCID 58575213HCID 58575213, compound

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Conditions

Temperature
0 °C

Procedure

To 70 mL of a solution of 1-benzyl-4-(pyrrolidin-1-yl)-1,2,3,6-tetrahydropyridine in benzene was added dropwise a solution 13 g of 4-bromoacetyl pyridine bromohydride in 150 mL of benzene at 0° C. over 1 hour, followed by stirring at 0° C. for 1 hour and then at room temperature for 15 hours. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (dichloromethane/methanol), and to the obtained 1.86 g of 1-benzyl-3-[2-oxo-2-(pyridin-4-yl)ethyl]piperidine-4-one were added 20 mL of acetic acid and 605 mg of ammonium acetate, followed by heating and refluxing for 1 hour. The reaction mixture was cooled to room temperature and the pH was adjusted to about 9 with a 10% aqueous sodium hydroxide solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (dichloromethane/methanol) to obtain 1.26 g of 5-benzyl-2-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine.

Workup

  1. waitat room temperature for 15 hours
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (dichloromethane/methanol)
  6. additionto the obtained 1.86 g of 1-benzyl-3-[2-oxo-2-(pyridin-4-yl)ethyl]piperidine-4-one were added 20 mL of acetic acid and 605 mg of ammonium acetate
  7. temperatureby heating
  8. temperaturerefluxing for 1 hour
  9. temperatureThe reaction mixture was cooled to room temperature
  10. extractionfollowed by extraction with ethyl acetate
  11. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  12. customthe solvent was evaporated under reduced pressure
  13. customThe obtained residue was purified by silica gel column chromatography (dichloromethane/methanol)

Sources & evidence

ORD record
ord-00985a74cac24c3881a9d74520b716fe
Source dataset
uspto-grants-2014_03
Patent number
US08674096B2

Reaction notes

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