Sodium hydride → (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopent-2-enyl)piperidin-2-one

HRID 932013Notes

Reaction equation

HRID 932013 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[NH:12][C:11](=[O:21])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Br[CH:25]1[CH2:29][CH2:28][CH:27]=[CH:26]1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[N:12]([CH:29]3[CH2:28][CH2:27][CH:26]=[CH:25]3)[C:11](=[O:21])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 111826803-BromocyclopenteneHCID 58573791(5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one

Product 1

HCID 58573261(5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopent-2-enyl)piperidin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3.25 g (10.16 mmol) of (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one (Example 1, Step E) in DMF (150 mL) at 0° C. was added a dispersion of 60% sodium hydride in mineral oil (1.016 g, 25.4 mmol). Evolution of gas was observed. The cloudy reaction mixture was stirred at 0° C. for 20 min before adding 3-bromocyclopent-1-ene (4.48 g, 30.5 mmol). The cloudy reaction mixture warmed to room temperature and stirred at room temperature for 18 h. The reaction was quenched with sat. aq. NH4Cl solution, diluted with EtOAc and the layers were separated. The organic layer was washed with 1M LiCl, sat. aq. NaCl solution, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent: 25 to 100% EtOAc in hexanes) to give the title compound as a 5:2 mixture of diastereomers.

Workup

  1. customThe cloudy reaction mixture
  2. customThe cloudy reaction mixture
  3. temperaturewarmed to room temperature
  4. stirringstirred at room temperature for 18 h
  5. customThe reaction was quenched with sat. aq. NH4Cl solution
  6. additiondiluted with EtOAc
  7. customthe layers were separated
  8. washThe organic layer was washed with 1M LiCl, sat. aq. NaCl solution
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by flash chromatography on silica gel (eluent: 25 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-bffe721751364d8baa6620c1f995f532
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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