Methylglyoxal → 1-(1-Ethoxycarbonyl-4-piperidinyl)-4-(4-fluorophenyl)-5-acetylimidazole

HRID 1979082Notes

Reaction equation

HRID 1979082 reaction equation
[CH:1](=O)[C:2]([CH3:4])=[O:3].[NH2:6][CH:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:9][CH2:8]1.C1(C)C=CC(S([CH:27]([N+:35]#[C-:36])[C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)(=O)=O)=CC=1.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.CCOC(C)=O>[CH2:16]([O:15][C:13]([N:10]1[CH2:9][CH2:8][CH:7]([N:6]2[C:1]([C:2](=[O:3])[CH3:4])=[C:27]([C:28]3[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=3)[N:35]=[CH:36]2)[CH2:12][CH2:11]1)=[O:14])[CH3:17]

Participants

7

Reactant 4

HCID 880MethylglyoxalHCID 11430Potassium CarbonateHCID 100867Ethyl 4-amino-1-piperidinecarboxylateHCID 10827289a-Tosyl-(4-fluorobenzyl) isocyanide

Product 1

HCID 99507171-(1-Ethoxycarbonyl-4-piperidinyl)-4-(4-fluorophenyl)-5-acetylimidazoleYield 75%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In an alternative procedure to that listed above, the title compound was prepared in the following manner: To a solution of pyruvaldehyde (40% w/w solution in water, 3.97 mL, 4.68 g, 25.94 mmol) in 34 mL of DMSO at room temperature was added dropwise ethyl 4-amino-piperidinecarboxylate (4.45 mL, 4.47 g, 25.94 mmol). After 10 min α-(p-toluenesulfonyl)-4-fluoro-benzylisonitrile (5.0 g, 17.3 mmol) and K2CO3 (2.39 g, 17.3 mmol) were added. After 15 h, the solution was diluted with 100 mL of EtOAc and washed with 2×100 mL of 3 N HCl. The aqueous layers were combined and basified with excess solid K2CO3 until the bubbling ceased. The aqueous layer was transferred to a separatory funnel and extracted 2×150 mL of EtOAc. The combined organics were washed with 3×75 mL of water and concentrated in vacuo to yield the imidazole product (4.65 g, 75%) which was used as is in subsequent steps.

Workup

  1. customwas prepared in the following manner
  2. washwashed with 2×100 mL of 3 N HCl
  3. customThe aqueous layer was transferred to a separatory funnel
  4. extractionextracted 2×150 mL of EtOAc
  5. washThe combined organics were washed with 3×75 mL of water
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4f7df31cdc234967861055441cb7464a
Source dataset
uspto-grants-2001_05
Patent number
US06239279B1

Reaction notes

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