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

HRID 727695Notes

Reaction equation

HRID 727695 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]([OH:29])=O)[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>[N:32]1([CH:37]2[CH2:42][CH2:41][N:40]([C:27]([C@@H:11]3[CH2:10][C@H:9]([S:8][CH2:7][C:6]4[CH:30]=[CH:31][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[CH2:13][N:12]3[C:14]([O:16][CH2:17][C:18]3[CH:19]=[CH:20][C:21]([N+:24]([O-:26])=[O:25])=[CH:22][CH:23]=3)=[O:15])=[O:29])[CH2:39][CH2:38]2)[CH:36]=[CH:35][N:34]=[CH:33]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

1520 mg of (2S,4S)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)-2-pyrrolidinecarboxylic acid were dissolved in 15 ml of dry acetonitrile, and 660 mg of N,N'-carbonyldiimidazole were added to the resulting solution, after which the mixture was stirred at room temperature for 30 minutes. At the end of this time, a solution of 538 mg of 4-(imidazol-1-yl)piperidine in 5 ml of dry acetonitrile was added to the resulting mixture, and the solution was stirred at room temperature for 30 minutes and then at 40° C. for 7 hours. The reaction mixture was then concentrated by evaporation under reduced pressure. The resulting residue was dissolved in ethyl acetate, washed with an aqueous solution of sodium hydrogencarbonate, with water and with an aqueous solution of sodium chloride, in that order, after which the mixture was dried over anhydrous sodium sulfate. The solvent was then removed by distillation under reduced pressure, and the resulting residue was subjected to column chromatography using a reverse phase silica gel column (Cosmosil 75C18 -PREP, 200 ml, manufactured by Nacalai Kagaku), eluted with mixtures of acetonitrile and water ranging from 50:50 to 55:45 by volume. The fractions containing the title compound were collected and concentrated by evaporation under reduced pressure, to obtain 1450 mg of the title compound as a powder.

Workup

  1. stirringthe solution was stirred at room temperature for 30 minutes
  2. waitat 40° C. for 7 hours
  3. concentrationThe reaction mixture was then concentrated by evaporation under reduced pressure
  4. dissolutionThe resulting residue was dissolved in ethyl acetate
  5. washwashed with an aqueous solution of sodium hydrogencarbonate, with water and with an aqueous solution of sodium chloride, in that order
  6. dry with materialafter which the mixture was dried over anhydrous sodium sulfate
  7. customThe solvent was then removed by distillation under reduced pressure
  8. washeluted with mixtures of acetonitrile and water ranging from 50:50 to 55:45 by volume
  9. additionThe fractions containing the title compound
  10. customwere collected
  11. concentrationconcentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-446f5defac4f4c40877158c7703779d5
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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