Hydrochloric Acid → (2S,4S)-4-Mercapto-2-{4-[2-(p-nitrobenzyloxycarbonyl)oxyethyl]-1-piperazinylcarbonyl}-1-(p-nitrobenzyloxycarbonyl)pyrrolidine

HRID 362090Notes

Reaction equation

Cl.C([S:5][C@@H:6]1[CH2:10][N:9]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=2)=[O:12])[C@H:8]([C:24]([N:26]2[CH2:31][CH2:30][N:29]([CH2:32][CH2:33][O:34][C:35]([O:37][CH2:38][C:39]3[CH:44]=[CH:43][C:42]([N+:45]([O-:47])=[O:46])=[CH:41][CH:40]=3)=[O:36])[CH2:28][CH2:27]2)=[O:25])[CH2:7]1)(=O)C>O1CCOCC1>[SH:5][C@@H:6]1[CH2:10][N:9]([C:11]([O:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([N+:21]([O-:23])=[O:22])=[CH:19][CH:20]=2)=[O:12])[C@H:8]([C:24]([N:26]2[CH2:27][CH2:28][N:29]([CH2:32][CH2:33][O:34][C:35]([O:37][CH2:38][C:39]3[CH:40]=[CH:41][C:42]([N+:45]([O-:47])=[O:46])=[CH:43][CH:44]=3)=[O:36])[CH2:30][CH2:31]2)=[O:25])[CH2:7]1

Participants

Conditions

Temperature: 50 °C

Procedure

600 ml of a 10% w/v methanolic solution of hydrogen chloride were added to a solution of 140 g of (2S,4S)-4-acetylthio-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-piperazinylcarbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidine [prepared as described in step 90(b)(ii) or 90(c)(ii) above] in 150 ml of 1,4-dioxane, and the resulting mixture was stirred at 50° C. for 1 hour. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and the concentrate was diluted with 1500 ml of ethyl acetate. The dilute solution was neutralized with an aqueous solution of sodium hydrogencarbonate and washed, in turn, with 300 ml of water and with 300 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 20:1 by volume as the eluent, to give 96.44 g of the title compound, as a colorless 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(a)(iii) above.

Workup

concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
additionthe concentrate was diluted with 1500 ml of ethyl acetate
washwashed, in turn, with 300 ml of water and with 300 ml of an aqueous solution of sodium chloride
customThe solvent was removed by distillation under reduced pressure
customthe resulting residue was purified by column chromatography through silica gel
washa gradient elution method

Sources & evidence

ORD record: ord-680f2b6f037f4499aaf80d3538ef2792
Source dataset: uspto-grants-1999_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05866564

Reaction notes

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