Water → 4-Methyl-4-(4-pyridin-3-yl-imidazol-1-yl)pentanoic acid methyl ester

HRID 353776Notes

Reaction equation

HRID 353776 reaction equation
[H-].[Na+].C(OP([CH2:11][C:12]([O:14][CH3:15])=[O:13])(OCC)=O)C.[CH3:16][C:17]([N:21]1[CH:25]=[C:24]([C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)[N:23]=[CH:22]1)([CH3:20])[CH:18]=O.O>C1COCC1>[CH3:15][O:14][C:12](=[O:13])[CH2:11][CH2:18][C:17]([CH3:20])([N:21]1[CH:25]=[C:24]([C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)[N:23]=[CH:22]1)[CH3:16]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 66113Methyl diethylphosphonoacetateHCID 235114292-Methyl-2-(4-pyridin-3-yl-imidazol-1-yl)-propionaldehyde

Product 1

HCID 207376634-Methyl-4-(4-pyridin-3-yl-imidazol-1-yl)pentanoic acid methyl esterYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of sodium hydride (1.2 eq) in THF was added slowly methyl diethylphosphonoacetate (1.2 eq) at 0° C. under dry conditions and the mixture was stirred at room temperature for 30 minutes. A solution of 2-Methyl-2-(4-pyridin-3-yl-imidazol-1-yl)-propionaldehyde (1 eq), in THF was added dropwise at room temperature and the mixture was stirred for 1 hour at the same temperature. The mixture was poured into H2O and the whole was extracted with ethyl acetate. The organic layer was washed with NaCl(sat), dried over sodium sulfate, filtered and concentrated. To a solution of the residue in ethyl acetate, was added Palladium, 10 wt. % on activated carbon and left stirring under 1 atm hydrogen overnight. After the catalyst was filtered off, the filtrate was purified by flash chromatography using a solvent gradient 97% DCM, 3% MeOH and 0.1% TEA to yield 4-Methyl-4-(4-pyridin-3-yl-imidazol-1-yl)pentanoic acid methyl ester (75%). MH+(274).

Workup

  1. stirringthe mixture was stirred for 1 hour at the same temperature
  2. extractionthe whole was extracted with ethyl acetate
  3. washThe organic layer was washed with NaCl(sat)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionTo a solution of the residue in ethyl acetate, was added Palladium, 10 wt. % on activated carbon
  8. waitleft
  9. stirringstirring under 1 atm hydrogen overnight
  10. filtrationAfter the catalyst was filtered off
  11. customthe filtrate was purified by flash chromatography

Sources & evidence

ORD record
ord-baad2247e57644ae9cbe0e451745600a
Source dataset
uspto-grants-2004_06
Patent number
US06756359B2

Reaction notes

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