Sodium Carbonate → 1-Ethoxycarbonyl-4-(4-fluoro-2-nitroanilino)piperidine

HRID 618376

Reaction equation

HRID 618376 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]1.Cl[C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=1[N+:21]([O-:23])=[O:22].C(=O)([O-])[O-].[Na+].[Na+].FC1C=CC(F)=CC=1[N+]([O-])=O>C1(O)CCCCC1.CCOC(C)=O.CCOC(C)=O.CCCCCC>[CH2:11]([O:10][C:8]([N:5]1[CH2:4][CH2:3][CH:2]([NH:1][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[N+:21]([O-:23])=[O:22])[CH2:7][CH2:6]1)=[O:9])[CH3:12]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 676591-Chloro-4-fluoro-2-nitrobenzene2×HCID 677672,5-DifluoronitrobenzeneHCID 100867Ethyl 4-amino-1-piperidinecarboxylate

Product 1

HCID 137921621-Ethoxycarbonyl-4-(4-fluoro-2-nitroanilino)piperidine

Reagents, catalysts & solvents 3

HCID 7966CyclohexanolSolventHCID 8857Ethyl AcetateSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

A solution of ethyl 4-amino-1-piperidine carboxylate (9.0 g, 52 mmol.) and 2-chloro-5-fluoronitrobenzene (10.3 g, 58 mmol.) in cyclohexanol (30 mL) containing powdered sodium carbonate (6.1 g, 57 mmol.) was refluxed (>160° C.) for 30 hours or until no further reaction was indicated by tlc (30% EtOAc/hexane). (Alternatively, 2,5-difluoro-nitrobenzene can be used in place of the 2-chloro-5-fluoronitro-benzene). The deep reddish reaction mixture was cooled and diluted with EtOAc. This solution was washed with dil. aq. HCl (3×), water, and then the organic layer dried (anhydrous Na2SO4) and the solvent evaporated to give a red oil. This oil was flash chromatographed on a column of silica gel and the product eluted with a 10-25% EtOAc/hexane gradient. The appropriate fractions were combined, the solvents evaporated, and the residue triturated with 10% Et2O/hexane to give 1-ethoxycarbonyl-4-(4-fluoro-2-nitroanilino)-piperidine as a bright reddish-orange solid, mp: 115-116° C., which was used without further purification.

Workup

  1. temperaturewas refluxed (>160° C.) for 30 hours
  2. customuntil no further reaction
  3. customThe deep reddish reaction mixture
  4. temperaturewas cooled
  5. washThis solution was washed with dil. aq. HCl (3×), water
  6. dry with materialthe organic layer dried (anhydrous Na2SO4)
  7. customthe solvent evaporated
  8. customto give a red oil
  9. customchromatographed on a column of silica gel
  10. washthe product eluted with a 10-25% EtOAc/hexane gradient
  11. customthe solvents evaporated
  12. customthe residue triturated with 10% Et2O/hexane

Sources & evidence

ORD record
ord-331122e00e5b48ee96ad24e8a426d6ae
Source dataset
uspto-grants-1999_09
Patent number
US05952351

Linked notes

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