4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate → (4-nitrophenyl)methyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[(3S,5S)-1-[(4-nitrophenyl)methoxycarbonyl]-5-[4-[N-[(4-nitrophenyl)methoxycarbonyl]carbamimidoyl]piperazine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

HRID 727697Notes

Reaction equation

HRID 727697 reaction equation
C1([ClH]P([ClH]C2C=CC=CC=2)(Cl)=O)C=CC=CC=1.[OH:18][C@@H:19]([C@H:21]1[C:42](=[O:43])[N:23]2[CH:24]([C:29]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=3)=[O:30])[C:25](=O)[C@H:26]([CH3:27])[C@@H:22]12)[CH3:20].FC(F)(F)S(O)(=O)=O.[SH:52][C@@H:53]1[CH2:57][N:56]([C:58]([O:60][CH2:61][C:62]2[CH:67]=[CH:66][C:65]([N+:68]([O-:70])=[O:69])=[CH:64][CH:63]=2)=[O:59])[C@H:55]([C:71]([N:73]2[CH2:78][CH2:77][N:76]([C:79](=[NH:94])[NH:80][C:81]([O:83][CH2:84][C:85]3[CH:90]=[CH:89][C:88]([N+:91]([O-:93])=[O:92])=[CH:87][CH:86]=3)=[O:82])[CH2:75][CH2:74]2)=[O:72])[CH2:54]1>C(#N)C.C(N(C(C)C)CC)(C)C>[OH:18][C@@H:19]([C@H:21]1[C:42](=[O:43])[N:23]2[C:24]([C:29]([O:31][CH2:32][C:33]3[CH:34]=[CH:35][C:36]([N+:39]([O-:41])=[O:40])=[CH:37][CH:38]=3)=[O:30])=[C:25]([S:52][C@@H:53]3[CH2:57][N:56]([C:58]([O:60][CH2:61][C:62]4[CH:67]=[CH:66][C:65]([N+:68]([O-:70])=[O:69])=[CH:64][CH:63]=4)=[O:59])[C@H:55]([C:71]([N:73]4[CH2:78][CH2:77][N:76]([C:79](=[NH:94])[NH:80][C:81]([O:83][CH2:84][C:85]5[CH:86]=[CH:87][C:88]([N+:91]([O-:93])=[O:92])=[CH:89][CH:90]=5)=[O:82])[CH2:75][CH2:74]4)=[O:72])[CH2:54]3)[C@H:26]([CH3:27])[C@H:22]12)[CH3:20]

Participants

5

Reactant 2

HCID 572368784-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylateHCID 140386399CID 140386399

Product 1

HCID 141580154(4-nitrophenyl)methyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[(3S,5S)-1-[(4-nitrophenyl)methoxycarbonyl]-5-[4-[N-[(4-nitrophenyl)methoxycarbonyl]carbamimidoyl]piperazine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylateYield 60.6%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 81531DiisopropylethylamineSolvent2×

Procedure

290 μl of diphenylphosphoric acid chloride and 44 μl of diisopropylethylamine were added dropwise, whilst ice-cooling, to a solution of 471 mg of 4-nitrobenzyl (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 5 ml of dry acetonitrile, and the resulting mixture was stirred at the same temperature for 1 hour. At the end of this time, a solution of 910 mg of (2S,4S)-4-mercapto-2-[4-(4-nitrobenzyloxycarbonylamidino)piperazin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine trifluoromethanesulfonate (prepared as described in Preparation 92) in 7 ml of dry acetonitrile and 500 μl of diisopropylethylamine were added dropwise, whilst ice-cooling, to the mixture, and the resulting mixture was left to stand overnight at the same temperature. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and the resulting residue was diluted with ethyl acetate, after which the mixture was washed with an aqueous solution of sodium hydrogencarbonate, with water and with an aqueous solution of sodium chloride. The ethyl acetate layer was dehydrated over anhydrous sodium sulfate and concentrated by evaporation under reduced pressure. The resulting residue was subjected to silica gel column chromatography [silica gel 60 (Art. 9385), manufactured by Merck, 150 ml], eluted with mixtures of ethyl acetate and acetonitrile in proportions of 8:2, 7:3 and 6:4, in that order. The fractions containing the desired compound were collected and concentrated by evaporation under reduced pressure, to obtain 691 mg of the title compound, as an amorphous powder.

Workup

  1. temperaturecooling, to the mixture
  2. waitthe resulting mixture was left
  3. waitto stand overnight at the same temperature
  4. concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
  5. additionthe resulting residue was diluted with ethyl acetate
  6. washafter which the mixture was washed with an aqueous solution of sodium hydrogencarbonate, with water and with an aqueous solution of sodium chloride
  7. concentrationconcentrated by evaporation under reduced pressure
  8. washeluted with mixtures of ethyl acetate and acetonitrile in proportions of 8:2, 7:3 and 6:4, in that order
  9. additionThe fractions containing the desired compound
  10. customwere collected
  11. concentrationconcentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-2777181de15342bdacca06e5c2ed7b0c
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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