3-Bromopentane → (5R,6S)-5-(3-Chlorophenyl)-6-(5-chloropyridin-2-yl)-1-(pentan-3-yl)piperidin-2-one

HRID 932055Notes

Reaction equation

HRID 932055 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][N:15]=3)[NH:12][C:11](=[O:21])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.Br[CH:23]([CH2:26][CH3:27])[CH2:24][CH3:25].[H-].[Na+].C([O-])(O)=O.[Na+].[Na+].[Cl-]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[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][N:15]=3)[N:12]([CH:23]([CH2:26][CH3:27])[CH2:24][CH3:25])[C:11](=[O:21])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 157383-BromopentaneHCID 24758Sodium hydrideHCID 86660724trans 5-(3-Chlorophenyl)-6-(5-chloropyridin-2-yl)piperidin-2-oneHCID 86660726Sodium bicarbonate sodium chloride

Product 1

HCID 58573152(5R,6S)-5-(3-Chlorophenyl)-6-(5-chloropyridin-2-yl)-1-(pentan-3-yl)piperidin-2-one

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a degassed solution of (5R,6S)-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)piperidin-2-one (1.00 g, 3.11 mmol, Example 121, Step F), 3-bromopentane (6.0 ml, 48.1 mmol) and tetrabutylammonium iodide (3.45 g, 9.34 mmol) in dry DMF (5.2 ml) was added 1.25 g (31 mmol) of a dispersion of 60% sodium hydride in mineral oil at 0° C. The reaction was heated to 90° for 8 h. Sat. aq. NaHCO3/NaCl solution was added and the mixture was extracted with ethyl acetate. The organic layers were washed with water and sat. NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Purification of the residue by flash chromatography on silica gel (eluent: 25 to 50% EtOAc/hexanes which had been sparged with NH3 gas, gradient elution) provided the title compound.

Workup

  1. temperatureThe reaction was heated to 90° for 8 h
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layers were washed with water and sat. NaCl solution
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customPurification of the residue by flash chromatography on silica gel (eluent: 25 to 50% EtOAc/hexanes which had been sparged with NH3 gas, gradient elution)

Sources & evidence

ORD record
ord-1ad80ebff7c14657afd5fd97cb79be31
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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