Ammonium Chloride → Ethyl 1-benzyl-5,5-difluoro-4-oxopiperidine-3-carboxylate

HRID 451557Notes

Reaction equation

HRID 451557 reaction equation
[CH2:1]([N:8]([CH2:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:9][C:10]([F:17])([F:16])[C:11]([O:13]CC)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].[NH4+].[Cl-]>CN1C(=O)CCC1>[CH2:1]([N:8]1[CH2:9][C:10]([F:16])([F:17])[C:11](=[O:13])[CH:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:18]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 23665647Potassium tert-butoxideHCID 59442745Ethyl 3-(benzyl(3-ethoxy-3-oxopropyl)amino)-2,2-difluoropropanoate

Product 1

HCID 49761228Ethyl 1-benzyl-5,5-difluoro-4-oxopiperidine-3-carboxylateYield 60%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of ethyl 3-(benzyl(3-ethoxy-3-oxopropyl)amino)-2,2-difluoropropanoate (10.78 g, 31.4 mmol) in NMP (100 mL) at 0° C. was added potassium tert-butoxide (5.64 g, 50.2 mmol) and the reaction mixture stirred at room temperature for 2 days. The reaction mixture was cooled to 0° C. and aqueous NH4Cl solution was added. The aqueous phase was extracted with EtOAc. The combined organic layers were dried over Na2SO4 and the solvent was evaporated. The residue was purified by flash chromatography using a gradient EtOAc/Heptane 0-70% over 40 minutes to give the title compound as white solid (5.56 g, 60%).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. extractionThe aqueous phase was extracted with EtOAc
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. customthe solvent was evaporated
  5. customThe residue was purified by flash chromatography
  6. customover 40 minutes

Sources & evidence

ORD record
ord-dcf895ba3783482e8284fa963b906185
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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