1-Benzyl-4-piperidone → HCID 68967526, compound

HRID 1427003Notes

Reaction equation

HRID 1427003 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:10][CH2:11][C:12]([CH3:15])([CH3:14])[N:13]=2)=[CH:5][CH:4]=1.[CH2:16]([N:23]1[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[Cl-].[NH4+]>II.C(OCC)(=O)C.O1CCCC1>[CH2:16]([N:23]1[CH2:28][CH2:27][C:26]([C:3]2[CH:8]=[CH:7][C:6]([C:9]3[O:10][CH2:11][C:12]([CH3:15])([CH3:14])[N:13]=3)=[CH:5][CH:4]=2)([OH:29])[CH2:25][CH2:24]1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

8

Reactant 4

HCID 192201-Benzyl-4-piperidoneHCID 25517Ammonium ChlorideHCID 4033952-(4-Bromophenyl)-4,4-dimethyl-4,5-dihydrooxazoleHCID 5462224Magnesium

Product 1

HCID 68967526HCID 68967526, compoundYield 35%

Reagents, catalysts & solvents 3

HCID 807IodineCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Magnesium (3.10 g, 127 mmol), iodine (135 mg, 0.531 mmol), and 2-(4-bromophenyl)-4,5-dihydro-4,4-dimethyloxazole (27 g, 106 mmol) were added to tetrahydrofuran (120 mL), and the mixture was heated under reflux for 1 hour. This reaction mixture was cooled to mom temperature, then 1-benzyl-4-piperidone (21.7 mL, 117 mmol) was added, and the mixture was heated under reflux for 3 hours. The reaction mixture was cooled to room temperature and then a saturated aqueous ammonium chloride solution and ethyl acetate were added for partition. The aqueous layer was extracted with ethyl acetate, and then the organic layers were combined and washed serially with water and a saturated saline solution. The organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under vacuum and the resultant residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=3:1-1:1). The target fraction was concentrated under vacuum to obtain the title compound (13.4 g, 35%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 1 hour
  3. temperatureThis reaction mixture was cooled to mom temperature
  4. temperaturethe mixture was heated
  5. temperatureunder reflux for 3 hours
  6. customfor partition
  7. extractionThe aqueous layer was extracted with ethyl acetate
  8. washwashed serially with water
  9. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. customThe solvent was evaporated under vacuum
  12. customthe resultant residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=3:1-1:1)
  13. concentrationThe target fraction was concentrated under vacuum

Sources & evidence

ORD record
ord-8bc2c11f6aeb4fa588834a8eb4fa2c4c
Source dataset
uspto-grants-2015_01
Patent number
US08933099B2

Reaction notes

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