4-Cyano-4-(3,4-dichlorophenyl)-7-(tetrahydropyran-4-yloxy)-heptanoic Acid Ethyl Ester → 5-(3,4-Dichlorophenyl)-5-[3-(tetrahydropyran-4-yloxy)-propyl]-2-piperidone

HRID 394543Notes

Reaction equation

HRID 394543 reaction equation
C([O:3][C:4](=O)[CH2:5][CH2:6][C:7]([C:26]#[N:27])([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=1)[CH2:8][CH2:9][CH2:10][O:11][CH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)C>CCO.[NH4+].[OH-].[Ni]>[Cl:25][C:20]1[CH:19]=[C:18]([C:7]2([CH2:8][CH2:9][CH2:10][O:11][CH:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[CH2:26][NH:27][C:4](=[O:3])[CH2:5][CH2:6]2)[CH:23]=[CH:22][C:21]=1[Cl:24]

Participants

5

Reactant 1

HCID 158876524-Cyano-4-(3,4-dichlorophenyl)-7-(tetrahydropyran-4-yloxy)-heptanoic Acid Ethyl Ester

Product 1

HCID 158876535-(3,4-Dichlorophenyl)-5-[3-(tetrahydropyran-4-yloxy)-propyl]-2-piperidoneYield 84.8%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 702EthanolSolventHCID 14923Ammonium HydroxideSolvent

Procedure

Raney Ni is added to a solution of cyanoester (5) (8.5 g, 19.84 mmol) in absolute EtOH (200 mL) and concentrated NH4OH (40 mL). The mixture was subjected to a H2 (51.8 psi) Par for 64.5 hours. The reaction mixture was filtered through celite, and N2 gas was passed through the solution to remove NH3. EtOH was then evaporated, and water is azeotropically removed with toluene. The crude oil is purified by flash chromatography (Ch2Cl2-MeOH/95:5) to give a colorless solid (6.5 g, 84.8% yield), mp ˜45° C.

Workup

  1. filtrationThe reaction mixture was filtered through celite, and N2 gas
  2. customto remove NH3
  3. customEtOH was then evaporated
  4. customwater is azeotropically removed with toluene
  5. customThe crude oil is purified by flash chromatography (Ch2Cl2-MeOH/95:5)

Sources & evidence

ORD record
ord-7ba802a933334aa6aab0694fa4acc618
Source dataset
uspto-grants-2003_08
Patent number
US06602886B2

Reaction notes

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