1-(2-Hydroxyethyl)piperazine → (2S,4S)-2-[4-(2-hydroxyethyl)piperazinylcarbonyl]-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

HRID 1033688Notes

Reaction equation

HRID 1033688 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.[OH:32][CH2:33][CH2:34][N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1>C(#N)C>[OH:32][CH2:33][CH2:34][N:35]1[CH2:40][CH2:39][N:38]([C:27]([C@@H:11]2[CH2:10][C@H:9]([S:8][CH2:7][C:6]3[CH:30]=[CH:31][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[CH2:13][N:12]2[C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=2)=[O:15])=[O:28])[CH2:37][CH2:36]1

Participants

4

Reactant 2

HCID 76771-(2-Hydroxyethyl)piperazineHCID 15297071(2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-proline

Product 1

HCID 15282196(2S,4S)-2-[4-(2-hydroxyethyl)piperazinylcarbonyl]-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidineYield 91.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

10.9 g of N,N'-carbonyldiimidazole were added to a solution of 25.0 g of (2S,4S)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)-2-pyrrolidinecarboxylic acid in 200 ml of anhydrous acetonirile, and the resulting mixture was stirred at room temperature for 1 hour. At the end of this time, a solution of 10.9 g of 1-(2-hydroxyethyl)piperazine in 50 ml of anhydrous acetonitrile was added to the mixture, which was then stirred at room temperature for 45 minutes. The reaction mixture was then concentrated by evaporation under reduced pressure, and the resulting residue was diluted with 800 ml of ethyl acetate and then washed, three times with 200 ml of water, and then once with 150 ml of an aqueous solution of sodium chloride. The ethyl acetate layer was concentrated by evaporation under reduced pressure to a volume of 100 ml, and the crystals which precipitated were collected by filtration, to give 28.6 g of the title compound as colorless crystals, melting at 140°-141 ° C.

Workup

  1. stirringwas then stirred at room temperature for 45 minutes
  2. concentrationThe reaction mixture was then concentrated by evaporation under reduced pressure
  3. additionthe resulting residue was diluted with 800 ml of ethyl acetate
  4. washwashed
  5. concentrationThe ethyl acetate layer was concentrated by evaporation under reduced pressure to a volume of 100 ml
  6. customthe crystals which precipitated
  7. filtrationwere collected by filtration

Sources & evidence

ORD record
ord-907004a87fa1418cbf25627e717bee31
Source dataset
uspto-grants-1994_05
Patent number
US05310735

Reaction notes

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