(2S,4S)-4-acetylthio-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine → (2S,4S)-4-Acetylthio-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-piperazinylcarbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

HRID 727688Notes

Reaction equation

HRID 727688 reaction equation
[C:1]([S:4][C@@H:5]1[CH2:9][N:8]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=2)=[O:11])[C@H:7]([C:23]([N:25]2[CH2:30][CH2:29][N:28]([CH2:31][CH2:32][OH:33])[CH2:27][CH2:26]2)=[O:24])[CH2:6]1)(=[O:3])[CH3:2]>C(Cl)Cl.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[C:1]([S:4][C@@H:5]1[CH2:9][N:8]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=2)=[O:11])[C@H:7]([C:23]([N:25]2[CH2:30][CH2:29][N:28]([CH2:31][CH2:32][O:33][C:10]([O:12][CH2:13][C:14]3[CH:15]=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=3)=[O:11])[CH2:27][CH2:26]2)=[O:24])[CH2:6]1)(=[O:3])[CH3:2]

Participants

5

Reactant 1

HCID 86752004(2S,4S)-4-acetylthio-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

Product 1

HCID 57136373(2S,4S)-4-Acetylthio-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-piperazinylcarbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidineYield 166.2%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1.10 g of N-nitrobenzyl chloroformate in 10 ml of methylene chloride was added, whilst ice-cooling, to a solution of 1.63 g of (2S,4S)-4-acetylthio-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine and 0.62 g of 4-dimethylaminopyridine in 15 ml of methylene chloride and the resulting mixture was stirred at the same temperature for 2 hours. At the end of this time, the reaction mixture was diluted with 100 ml of ethyl acetate, and the dilute solution was washed, in turn, with 100 ml of an aqueous solution of sodium hydrogencarbonate, with 100 ml of water and with 100 ml of an aqueous solution of sodium chloride. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through silica gel, using a gradient elution method, with mixtures of ethyl acetate and methanol ranging from 30:1 to 25:1 by volume as the eluent to give 1.86 g of the title compound, as a powder. The infrared absorption spectrum and nuclear magnetic resonance spectrum of the compound thus obtained were identical with those of the compound prepared as described in step 90(b)(ii) above.

Workup

  1. washthe dilute solution was washed, in turn, with 100 ml of an aqueous solution of sodium hydrogencarbonate, with 100 ml of water and with 100 ml of an aqueous solution of sodium chloride
  2. customThe solvent was removed by distillation under reduced pressure
  3. customthe resulting residue was purified by column chromatography through silica gel
  4. washa gradient elution method

Sources & evidence

ORD record
ord-07779c829c104e5aa76174fd9d9dd2fa
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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