1-Benzyl-4-piperidone → HCID 11196326, compound

HRID 2265140Notes

Reaction equation

HRID 2265140 reaction equation
[C:1]1([CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[Mg]Br.O1CCCC1.[CH2:15]([N:22]1[CH2:27][CH2:26][C:25](=O)[CH2:24][CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:15]([N:22]1[CH2:27][CH:26]=[C:25]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[CH3:9])[CH2:24][CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 192201-Benzyl-4-piperidoneHCID 25517Ammonium ChlorideHCID 178420638HCID 178420638, compound

Product 1

HCID 11196326HCID 11196326, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

600 mL of 0.5 M o-tolylmagnesium bromide-tetrahydrofuran solution was cooled to 0° C., and 200 mL of tetrahydrofuran solution of 40.0 g of 1-benzylpiperidin-4-one was dropwise added thereto, over 10 minutes. Cooled with ice, the reaction mixture was stirred further for 30 minutes. Then, aqueous saturated ammonium chloride solution was added thereto to stop the reaction, and this was extracted three times with ethyl acetate. The organic layer was washed with saturated saline water, dried with anhydrous magnesium sulfate, and the solvent was evaporated off under reduced pressure. 300 mL of trifluoroacetic acid was added to the resulting residue, heated up to 80° C., and stirred for 2 hours. The reaction liquid was concentrated under reduced pressure, the residue was neutralized with aqueous saturated sodium hydrogencarbonate solution, and then extracted with ethyl acetate. The organic layer was washed with saturated saline water, dried with anhydrous magnesium sulfate, and the solvent was evaporated off under reduced pressure. The residue was separated and purified through silica gel column chromatography (hexane/ethyl acetate=20/1 to 10/1) to obtain 39.9 g of the entitled compound as a pale brown oily substance.

Workup

  1. temperatureCooled with ice
  2. customthe reaction
  3. extractionthis was extracted three times with ethyl acetate
  4. washThe organic layer was washed with saturated saline water
  5. dry with materialdried with anhydrous magnesium sulfate
  6. customthe solvent was evaporated off under reduced pressure
  7. addition300 mL of trifluoroacetic acid was added to the resulting residue
  8. stirringstirred for 2 hours
  9. customThe reaction liquid
  10. concentrationwas concentrated under reduced pressure
  11. extractionextracted with ethyl acetate
  12. washThe organic layer was washed with saturated saline water
  13. dry with materialdried with anhydrous magnesium sulfate
  14. customthe solvent was evaporated off under reduced pressure
  15. customThe residue was separated
  16. custompurified through silica gel column chromatography (hexane/ethyl acetate=20/1 to 10/1)

Sources & evidence

ORD record
ord-bf27e752f7f445c789475a4a9162ffb7
Source dataset
uspto-grants-2010_12
Patent number
US07855294B2

Reaction notes

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