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

HRID 2257518Notes

Reaction equation

HRID 2257518 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>[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

6

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-acetylimidazole

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of pyruvaldehyde (40% w/w solution in water, 6.6 mL, 7.8 g, 0.058 mol) in DMSO (100 mL) at ambient temperature was added ethyl 4-aminopiperidinecarboxylate (10 g, 0.058 mol). After 10 min, α-(p-toluenesulfonyl)-4-fluorobenzylisonitrile (8.4 g, 0.029 mol) and K2CO3 (8.0 g, 0.058 mol) were added. After stirring for 18 h, the solution was partition between EtOAc and 3N HCl and the organic phase was washed with 3N HCl. The combined aqueous layers were neutralized with solid K2CO3 and extracted twice with EtOAc. The combined organics were washed with brine, dried (MgSO4) and concentrated in vacuo to give a brown oil which solidified upon standing. Flash chromatography eluting consecutively with 33%, 50% and 67% EtOAc in hexanes followed by trituration with ether afforded the title compound as a white solid; yield 3.5 g (23%).

Workup

  1. customthe solution was partition between EtOAc and 3N HCl
  2. washthe organic phase was washed with 3N HCl
  3. extractionextracted twice with EtOAc
  4. washThe combined organics were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customto give a brown oil which
  8. washFlash chromatography eluting consecutively with 33%, 50% and 67% EtOAc in hexanes

Sources & evidence

ORD record
ord-d3b85dd859c149e79969657d65263d61
Source dataset
uspto-grants-1997_08
Patent number
US05658903

Reaction notes

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