4-Nitrobenzyl chloroformate → HCID 86751996, compound

HRID 727641Notes

Reaction equation

HRID 727641 reaction equation
C(N(C(C)C)CC)(C)C.Cl.[CH3:11][O:12][C:13]1[CH:46]=[CH:45][C:16]([CH2:17][S:18][C@@H:19]2[CH2:23][N:22]([C:24]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][C:31]([N+:34]([O-:36])=[O:35])=[CH:30][CH:29]=3)=[O:25])[C@H:21]([C:37]([NH:39][C@H:40]3[CH2:44][CH2:43][NH:42][CH2:41]3)=[O:38])[CH2:20]2)=[CH:15][CH:14]=1.Cl[C:48]([O:50][CH2:51][C:52]1[CH:57]=[CH:56][C:55]([N+:58]([O-:60])=[O:59])=[CH:54][CH:53]=1)=[O:49]>CN(C)C1C=CN=CC=1.C(#N)C>[CH3:11][O:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:17][S:18][C@@H:19]2[CH2:23][N:22]([C:24]([O:26][CH2:27][C:28]3[CH:29]=[CH:30][C:31]([N+:34]([O-:36])=[O:35])=[CH:32][CH:33]=3)=[O:25])[C@H:21]([C:37]([NH:39][C@H:40]3[CH2:44][CH2:43][N:42]([C:48]([O:50][CH2:51][C:52]4[CH:53]=[CH:54][C:55]([N+:58]([O-:60])=[O:59])=[CH:56][CH:57]=4)=[O:49])[CH2:41]3)=[O:38])[CH2:20]2)=[CH:45][CH:46]=1

Participants

6

Reactant 3

HCID 782054-Nitrobenzyl chloroformate2×HCID 81531DiisopropylethylamineHCID 67585366HCID 67585366, compound

Product 1

HCID 86751996HCID 86751996, compoundYield 68.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent3×

Conditions

Temperature
0 °C

Procedure

230 mg of diisopropylethylamine were added to a suspension of 1.0 g of (2S,4S)-4-(4-methoxybenzylthio)-2-[(3S)-pyrrolidin-3-ylaminocarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine hydrochloride [prepared as described in step (ii) above] and 240 mg of 4-dimethylaminopyridine in 10 ml of dry acetonitrile, and the resulting mixture was cooled to 0° C. A solution of 430 mg of 4-nitrobenzyl chloroformate in 4 ml of dry acetonitrile was then added to the mixture. The mixture was then stirred at room temperature for 3 hours, after which a solution of 117 mg of 4-nitrobenzyl chloroformate in 2 ml of dry acetonitrile was added and the mixture was stirred at the same temperature for 1 hour. At the end of this time, the reaction mixture was freed from the solvent by distillation under reduced pressure, and the residue was diluted with 50 ml of methylene chloride. The diluted solution was washed with a saturated aqueous solution of sodium chloride. The aqueous washings were extracted with methylene chloride. The organic extract and the methylene chloride solution were combined and dried over anhydrous magnesium sulfate, and then the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel, using a 4:1 by volume mixture of methylene chloride and acetonitrile as the eluent, to give 862 mg of the title compound as a powder.

Workup

  1. stirringthe mixture was stirred at the same temperature for 1 hour
  2. distillationAt the end of this time, the reaction mixture was freed from the solvent by distillation under reduced pressure
  3. additionthe residue was diluted with 50 ml of methylene chloride
  4. washThe diluted solution was washed with a saturated aqueous solution of sodium chloride
  5. extractionThe aqueous washings were extracted with methylene chloride
  6. extractionThe organic extract
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was removed by distillation under reduced pressure
  9. customThe resulting residue was purified by column chromatography through silica gel
  10. additionby volume mixture of methylene chloride and acetonitrile as the eluent

Sources & evidence

ORD record
ord-c0f662879ea84fdea428db8279be6761
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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