Acetic Acid → trans-6-(2,5-Difluorophenyl)-1-benzyl-5-nitropiperidin-2-one

HRID 241573

Reaction equation

HRID 241573 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:3]=1[CH:4]=O.[N+:11]([CH2:14][CH2:15][CH2:16][C:17]([O:19]C)=O)([O-:13])=[O:12].[CH2:21]([NH2:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C([O-])(=O)C.[Na+].C(O)(=O)C>C(O)C>[F:1][C:2]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:3]=1[C@@H:4]1[N:28]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:17](=[O:19])[CH2:16][CH2:15][C@H:14]1[N+:11]([O-:13])=[O:12]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 7504BenzylamineHCID 25604Methyl 4-nitrobutyrateHCID 1376632,5-DifluorobenzaldehydeHCID 517045Sodium Acetate

Product 1

HCID 67388890trans-6-(2,5-Difluorophenyl)-1-benzyl-5-nitropiperidin-2-one

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 2,5-difluorobenzaldehyde (1.09 g, 7.67 mmol) in ethanol (20 mL) were added methyl 4-nitrobutyrate (1.13 g, 7.04 mmol), benzylamine (0.98 mL, 7.67 mmol), sodium acetate (1.26 g, 15.3 mmol) and acetic acid (0.88 mL, 15.4 mmol). The mixture was stirred at rt for 12 h and then heated at reflux temperature overnight. After evaporation, the residue was purified by column chromatography (silica gel Biotage 40M™) eluting with ethyl acetate/hexane (gradient from 3% to 50%) to give the title compound as the racemic trans isomer. LC-MS: 347.1 (M+1).

Workup

  1. temperatureheated
  2. temperatureat reflux temperature overnight
  3. customAfter evaporation
  4. customthe residue was purified by column chromatography (silica gel Biotage 40M™)
  5. washeluting with ethyl acetate/hexane (gradient from 3% to 50%)

Sources & evidence

ORD record
ord-9c81f34126db454a9c58bf2b4af6f2ab
Source dataset
uspto-grants-2014_02
Patent number
US08653059B2

Linked notes

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