Triethylamine → (2R,4R)-4-Hydroxy-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-piperazinylcarbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

HRID 727679Notes

Reaction equation

HRID 727679 reaction equation
P(C#N)(OCC)(OCC)=O.C(N(CC)CC)C.[OH:18][C@H:19]1[CH2:23][N:22]([C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([N+:34]([O-:36])=[O:35])=[CH:30][CH:29]=2)=[O:25])[C@@H:21]([C:37]([OH:39])=O)[CH2:20]1.Cl.Cl.[N+:42]([C:45]1[CH:63]=[CH:62][C:48]([CH2:49][O:50][C:51]([O:53][CH2:54][CH2:55][N:56]2[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]2)=[O:52])=[CH:47][CH:46]=1)([O-:44])=[O:43]>CN(C)C=O.C(OCC)(=O)C>[OH:18][C@H:19]1[CH2:23][N:22]([C:24]([O:26][CH2:27][C:28]2[CH:29]=[CH:30][C:31]([N+:34]([O-:36])=[O:35])=[CH:32][CH:33]=2)=[O:25])[C@@H:21]([C:37]([N:59]2[CH2:60][CH2:61][N:56]([CH2:55][CH2:54][O:53][C:51]([O:50][CH2:49][C:48]3[CH:62]=[CH:63][C:45]([N+:42]([O-:44])=[O:43])=[CH:46][CH:47]=3)=[O:52])[CH2:57][CH2:58]2)=[O:39])[CH2:20]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 22881682cis-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)-D-prolineHCID 675853301-[2-(4-Nitrobenzyloxycarbonyloxy)ethyl]piperazine dihydrochloride

Product 1

HCID 86752007(2R,4R)-4-Hydroxy-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-piperazinylcarbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidineYield 65.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3.34 ml of diethyl cyanophosphate and 8.92 ml of triethylamine were added, whilst ice-cooling, to a suspension of 6.2 g of cis-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)-D-proline and 8.41 g of 1-[2-(4-nitrobenzyloxycarbonyloxy)ethyl]piperazine dihydrochloride in 62 ml of dry dimethylformamide, and the resulting mixture was stirred at the same temperature for 30 minutes. At the end of this time, the reaction mixture was diluted with 250 ml of ethyl acetate, and the dilute solution was washed with water and then dried over anhydrous magnesium sulfate. The mixture was concentrated by evaporation under reduced pressure, and the resulting residue was purified by column chromatography through silica gel, using a 4:1 by volume mixture of ethyl acetate and methanol as the eluent, to give 7.84 g of the title compound, as an oil.

Workup

  1. washthe dilute solution was washed with water
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationThe mixture was concentrated by evaporation under reduced pressure
  4. customthe resulting residue was purified by column chromatography through silica gel
  5. additionby volume mixture of ethyl acetate and methanol as the eluent

Sources & evidence

ORD record
ord-f09724d77b3b4308aed461f5cf944cf3
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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