Trichloroacetyl isocyanate → (2S,4S)-2-[4-(2-carbamoyloxyethyl)-1-piperazinylcarbonyl]-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

HRID 362067Notes

Reaction equation

HRID 362067 reaction equation
ClC(Cl)(Cl)[C:3]([N:5]=C=O)=[O:4].[OH:10][CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][N:16]([C:19]([C@@H:21]2[CH2:25][C@H:24]([S:26][CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)[CH2:23][N:22]2[C:36]([O:38][CH2:39][C:40]2[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][CH:41]=2)=[O:37])=[O:20])[CH2:15][CH2:14]1>C(Cl)Cl>[C:3]([O:10][CH2:11][CH2:12][N:13]1[CH2:14][CH2:15][N:16]([C:19]([C@@H:21]2[CH2:25][C@H:24]([S:26][CH2:27][C:28]3[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=3)[CH2:23][N:22]2[C:36]([O:38][CH2:39][C:40]2[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][CH:41]=2)=[O:37])=[O:20])[CH2:17][CH2:18]1)(=[O:4])[NH2:5]

Participants

4

Reactant 2

HCID 76400Trichloroacetyl isocyanateHCID 15282196(2S,4S)-2-[4-(2-hydroxyethyl)piperazinylcarbonyl]-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

Product 1

HCID 57049434(2S,4S)-2-[4-(2-carbamoyloxyethyl)-1-piperazinylcarbonyl]-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1.43 ml of trichloroacetyl isocyanate were added, whilst ice-cooling, to a solution of 5.59 g of (2S,4S)-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine [prepared as described in step (i) above] in 50 ml of dry methylene chloride, and the resulting mixture was stirred at the same temperature for 30 minutes. At the end of this time, the solvent was removed by distillation under reduced pressure, and the resulting residue was dissolved in 120 ml of methanol. This solution was then stirred at room temperature for 4.5 hours in the presence of 35 g of silica gel (Merck, silica gel 60, 230-400 mesh). The silica gel was removed by filtration and the filtrate was freed from the solvent. The residue was purified by column chromatography through silica gel, using a 8:1 by volume mixture of ethyl acetate and methanol as the eluent, to give 5.76 g of the title compound as a colorless powder.

Workup

  1. customAt the end of this time, the solvent was removed by distillation under reduced pressure
  2. dissolutionthe resulting residue was dissolved in 120 ml of methanol
  3. stirringThis solution was then stirred at room temperature for 4.5 hours in the presence of 35 g of silica gel (Merck, silica gel 60, 230-400 mesh)
  4. customThe silica gel was removed by filtration
  5. customThe residue was purified by column chromatography through silica gel
  6. additionby volume mixture of ethyl acetate and methanol as the eluent

Sources & evidence

ORD record
ord-2965266baaa54557a2ea44d911c84fea
Source dataset
uspto-grants-1999_02
Patent number
US05866564

Reaction notes

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