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

HRID 727672Notes

Reaction equation

HRID 727672 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 6342AcetonitrileSolvent2×

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 dry acetonitrile, and the resulting mixture was stirred at room temperature for 1 hour. A solution of 10.9 g of 1-(2-hydroxyethyl)piperazine in 50 ml of dry acetonitrile was added to the reaction mixture, and the resulting mixture was stirred at room temperature for 45 minutes. An the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, after which it was diluted with 800 ml of ethyl acetate. The dilute solution was washed, in turn, with water (200 ml, three times) and an aqueous solution of sodium chloride (150 ml, once). The resulting ethyl acetate solution 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. stirringthe resulting mixture was stirred at room temperature for 45 minutes
  2. concentrationAn the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
  3. additionafter which it was diluted with 800 ml of ethyl acetate
  4. washThe dilute solution was washed, in turn, with water (200 ml, three times)
  5. concentrationThe resulting ethyl acetate solution 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-7e80c4821d77474ca8843262e1e0c526
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

Loading…