p-Toluenesulfonic acid → HCID 12364533, compound

HRID 522870Notes

Reaction equation

HRID 522870 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1CCOCC1.CC1C=CC(S(O)(=O)=O)=CC=1.[CH2:32](Br)[C:33]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:34]>C1C=CC=CC=1.O>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH:10]([CH2:32][C:33](=[O:34])[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 6259Phenacyl bromideHCID 8083MorpholineHCID 192201-Benzyl-4-piperidone

Product 1

HCID 12364533HCID 12364533, compoundYield 27,674%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolvent2×HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-benzylpiperidin-4-one (10.0 g, 0.0529 mmol) and morpholine (6.9 g, 0.079 mol) in dry benzene was added a catalytic amount of PTSA (450 mg, 0.00262 mol). A round bottom flask was attached with a Dean Stark assembly then the reaction mixture was heat at reflux under nitrogen for 17 to 18 h. The reaction mixture was concentrated under a nitrogen atmosphere, then the crude mixture was diluted with dry benzene and cooled to 0° C. and a solution of phenacyl bromide (12.63 g, 0.0634 mol) in benzene was added. The reaction mixture was allowed to warm to RT and stirred overnight. The reaction mixture was diluted with water and stirred at RT for 1 h, then extracted with EtOAc (300×3 mL), dried over Na2SO4 and concentrated to afford the crude product which was purified by flash chromatography (eluent: 10% EtOAc/hexanes) to afford 1-benzyl-3-(2-oxo-2-phenylethyl)-piperidin-4-one (4.5 g, 45.0%).

Workup

  1. customA round bottom flask was attached with a Dean Stark
  2. temperatureassembly then the reaction mixture was heat
  3. temperatureat reflux under nitrogen for 17 to 18 h
  4. concentrationThe reaction mixture was concentrated under a nitrogen atmosphere
  5. additionthe crude mixture was diluted with dry benzene
  6. temperatureto warm to RT
  7. stirringstirred at RT for 1 h
  8. extractionextracted with EtOAc (300×3 mL)
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customto afford the crude product which
  12. customwas purified by flash chromatography (eluent: 10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-681863e8f75b4f109d9ae73a65856499
Source dataset
uspto-grants-2016_05
Patent number
US09334269B2

Reaction notes

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