Cesium carbonate → Methyl 1-(5-formyl-2-nitrophenyl)piperidine-4-carboxylate

HRID 1801590Notes

Reaction equation

HRID 1801590 reaction equation
F[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH:5]=[O:6].[NH:13]1[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:15][CH2:14]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.CCOC(C)=O>[CH:5]([C:4]1[CH:7]=[CH:8][C:9]([N+:10]([O-:12])=[O:11])=[C:2]([N:13]2[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:15][CH2:14]2)[CH:3]=1)=[O:6]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 424914Methyl isonipecotateHCID 38081203-Fluoro-4-nitrobenzaldehyde

Product 1

HCID 59803194Methyl 1-(5-formyl-2-nitrophenyl)piperidine-4-carboxylateYield 68%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-fluoro-4-nitrobenzaldehyde 63 (0.793 g, 5 mmol) in DMSO (5 mL) was added methyl piperidine-4-carboxylate (0.7 mL, 5 mmol) and cesium carbonate (1.76 g, 5 mmol). The reaction mixture was stirred at room temperature for 30 min, heated to 70° C. for 2 h, and diluted with EtOAc. The organic phase was washed with water (1×), brine (1×), dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel (eluted with 30% to 60% EtOAc in hexanes) gave methyl 1-(5-formyl-2-nitrophenyl)piperidine-4-carboxylate 64 (0.931 g, 68% yield) as a yellow oil. Mass spectrum: calculated for C14H16N2O5 292.1. found 293.1 (M++1).

Workup

  1. temperatureheated to 70° C. for 2 h
  2. washThe organic phase was washed with water (1×), brine (1×)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash column chromatography on silica gel (eluted with 30% to 60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-68752f7b6e06408ab45812490aaeb160
Source dataset
uspto-grants-2013_01
Patent number
US08349831B2

Reaction notes

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