4-Nitrobenzyl chloroformate → (2S, 4S)-4-(4-Methoxybenzylthio)-2-[3-(4-nitrobenzyloxycarbonylamino)azetidin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

HRID 727724Notes

Reaction equation

HRID 727724 reaction equation
[NH2:1][CH:2]1[CH2:5][N:4]([C:6]([C@@H:8]2[CH2:12][C@H:11]([S:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[CH2:10][N:9]2[C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=2)=[O:24])=[O:7])[CH2:3]1.C(N(C(C)C)CC)(C)C.Cl[C:46]([O:48][CH2:49][C:50]1[CH:55]=[CH:54][C:53]([N+:56]([O-:58])=[O:57])=[CH:52][CH:51]=1)=[O:47]>C(Cl)Cl.C(OCC)(=O)C>[CH3:22][O:21][C:18]1[CH:17]=[CH:16][C:15]([CH2:14][S:13][C@@H:11]2[CH2:10][N:9]([C:23]([O:25][CH2:26][C:27]3[CH:28]=[CH:29][C:30]([N+:33]([O-:35])=[O:34])=[CH:31][CH:32]=3)=[O:24])[C@H:8]([C:6]([N:4]3[CH2:5][CH:2]([NH:1][C:46]([O:48][CH2:49][C:50]4[CH:51]=[CH:52][C:53]([N+:56]([O-:58])=[O:57])=[CH:54][CH:55]=4)=[O:47])[CH2:3]3)=[O:7])[CH2:12]2)=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 782054-Nitrobenzyl chloroformateHCID 81531DiisopropylethylamineHCID 11145523(2S,4S)-2-(3-Aminoazetidin-1-ylcarbonyl)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

Product 1

HCID 10952523(2S, 4S)-4-(4-Methoxybenzylthio)-2-[3-(4-nitrobenzyloxycarbonylamino)azetidin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidineYield 58.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

0.81 g of (2S,4S)-2-(3-aminoazetidin-1-ylcarbonyl)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine [prepared as described in step (a) above] was dissolved in 20 ml of methylene chloride, and 0.32 g of diisopropylethylamine and 0.40 g of p-nitrobenzyl chloroformate were added to the resulting solution, whilst ice-cooling. The resulting mixture was then stirred at the same temperature for 40 minutes. At the end of this time, the reaction mixture was diluted with ethyl acetate and washed with water and with an aqueous solution of sodium chloride, in that order. The ethyl acetate layer was dried over anhydrous magnesium sulfate and concentrated by evaporation under reduced pressure. The residue was subjected to silica gel column chromatography (silica gel 60 9385, manufactured by Merck, 40 g) to give 0.64 g of the title compound, in the form of an amorphous powder, from the fraction obtained by solution with a 99:1 by volume mixture of ethyl acetate and methanol.

Workup

  1. temperaturecooling
  2. washwashed with water and with an aqueous solution of sodium chloride, in that order
  3. dry with materialThe ethyl acetate layer was dried over anhydrous magnesium sulfate
  4. concentrationconcentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-ea3d86f36f6949bc9da3655d6b747292
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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