(2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-proline → HCID 67585037, compound

HRID 727663Notes

Reaction equation

HRID 727663 reaction equation
[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][S:8][C@@H:9]2[CH2:13][N:12]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=3)=[O:15])[C@H:11]([C:27](O)=[O:28])[CH2:10]2)=[CH:5][CH:4]=1.[N:32]1([CH:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)[CH:36]=[CH:35][N:34]=[CH:33]1>C(#N)C>[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][S:8][C@@H:9]2[CH2:13][N:12]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=3)=[O:15])[C@H:11]([C:27]([N:40]3[CH2:39][CH2:38][CH:37]([N:32]4[CH:36]=[CH:35][N:34]=[CH:33]4)[CH2:42][CH2:41]3)=[O:28])[CH2:10]2)=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 15297071(2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-prolineHCID 157899224-(1H-Imidazol-1-yl)piperidine

Product 1

HCID 67585037HCID 67585037, compoundYield 73.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

660 mg of N,N'-carbonyldiimidazole were added to a solution of 1.52 g of (2S,4S)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)-2-pyrrolidinecarboxylic acid in 15 ml of dry acetonitrile, and the resulting mixture was stirred at room temperature for 30 minutes. A solution of 538 mg of 4-(imidazol-1-yl)piperidine in 5 ml of dry acetonitrile was then added to the solution, and the mixture was stirred at room temperature for 30 minutes and then at 40° C. for a further 7 hours. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and the residue was dissolved in ethyl acetate. The resulting solution was washed with an aqueous solution of sodium hydrogen-carbonate, with water and with an aqueous solution of sodium chloride, in that order. The organic solution was then dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by reverse phase column chromatography through 200 ml of Cosmo Sil 75C18 -PREP (a trade mark for a product of Nacalai Tesque), using a gradient elution method, with mixtures of acetonitrile and water ranging from 50:50 to 45 by volume as the eluent. Those fractions containing the title compound were combined and concentrated by evaporation under reduced pressure, to give 1.45 g of the title compound, as a powder.

Workup

  1. stirringthe mixture was stirred at room temperature for 30 minutes
  2. waitat 40° C. for a further 7 hours
  3. concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
  4. dissolutionthe residue was dissolved in ethyl acetate
  5. washThe resulting solution was washed with an aqueous solution of sodium hydrogen-carbonate, with water and with an aqueous solution of sodium chloride, in that order
  6. dry with materialThe organic solution was then dried over anhydrous sodium sulfate
  7. customthe solvent was removed by distillation under reduced pressure
  8. customThe residue was purified by reverse phase column chromatography through 200 ml of Cosmo Sil 75C18 -PREP (a trade mark for a product of Nacalai Tesque),
  9. washa gradient elution method
  10. additionThose fractions containing the title compound
  11. concentrationconcentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-2665b240416a4ffb933ccbca66311a8f
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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