Sodium hydride → (S)-Ethyl 2-((2S,3R)-3-(3-chlorophenyl)-2-(4-chlorophenyl)-6-oxopiperidin-1-yl)butanoate

HRID 1048206Notes

Reaction equation

HRID 1048206 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]([CH2:31][CH3:32])[C:26]([O:28][CH2:29][CH3:30])=[O:27].[NH4+].[Cl-]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:9][CH2:10][C:11](=[O:21])[N:12]([C@@H:25]([CH2:31][CH3:32])[C:26]([O:28][CH2:29][CH3:30])=[O:27])[C@@H:13]2[C:14]2[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 79039Butanoic acid, 2-bromo-, ethyl esterHCID 58573791(5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one

Product 1

HCID 60154117(S)-Ethyl 2-((2S,3R)-3-(3-chlorophenyl)-2-(4-chlorophenyl)-6-oxopiperidin-1-yl)butanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 15 g (46.8 mmol) of ((5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one (Example 1, Step E) in 140 mL of DMF was added 3.75 g (94 mmol) of a dispersion of 60% sodium hydride in mineral oil at 0° C. After being stirred for 20 min, ethyl 2-bromobutanoate (17.2 mL, 117 mmol) was added at 0° C. and the resulting solution was stirred at 25° C. for 12 h until completion of the reaction. Then sat. aq. NH4Cl solution was added and the mixture was extracted with ethyl acetate. The combined 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: 30% EtOAc/hexanes, gradient elution) provided the title compound as the faster eluting isomer.

Workup

  1. stirringthe resulting solution was stirred at 25° C. for 12 h until completion of the reaction
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe combined 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: 30% EtOAc/hexanes, gradient elution)

Sources & evidence

ORD record
ord-2af3aadd16dc4401bd36ecc415021a69
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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