Diphenylphosphinic chloride → 4-Nitrobenzyl (1R,5S,6S)-2-{(2S,4S)-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-1-methylpyrrolidin-4-ylthio}-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

HRID 727614Notes

Reaction equation

HRID 727614 reaction equation
C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(C(C)C)CC)(C)C.[OH:25][C@@H:26]([C@H:28]1[C:49](=[O:50])[N:30]2[CH:31]([C:36]([O:38][CH2:39][C:40]3[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][CH:41]=3)=[O:37])[C:32](=O)[C@H:33]([CH3:34])[C@@H:29]12)[CH3:27].FC(F)(F)S(O)(=O)=O.FC(F)(F)S(O)(=O)=O.[SH:67][C@@H:68]1[CH2:72][N:71]([CH3:73])[C@H:70]([C:74]([N:76]2[CH2:81][CH2:80][N:79]([CH2:82][CH2:83][OH:84])[CH2:78][CH2:77]2)=[O:75])[CH2:69]1>C(#N)C>[OH:84][CH2:83][CH2:82][N:79]1[CH2:80][CH2:81][N:76]([C:74]([C@@H:70]2[CH2:69][C@H:68]([S:67][C:32]3[C@H:33]([CH3:34])[C@@H:29]4[C@@H:28]([C@H:26]([OH:25])[CH3:27])[C:49](=[O:50])[N:30]4[C:31]=3[C:36]([O:38][CH2:39][C:40]3[CH:41]=[CH:42][C:43]([N+:46]([O-:48])=[O:47])=[CH:44][CH:45]=3)=[O:37])[CH2:72][N:71]2[CH3:73])=[O:75])[CH2:77][CH2:78]1

Participants

6

Reactant 4

HCID 73910Diphenylphosphinic chlorideHCID 81531Diisopropylethylamine2×HCID 572368784-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylateHCID 86753695(2S,4S)-4-Mercapto-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl)-1-methylpyrrolidine bis(trifluoromethanesulfonate)

Product 1

HCID 1317204294-Nitrobenzyl (1R,5S,6S)-2-{(2S,4S)-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-1-methylpyrrolidin-4-ylthio}-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylateYield 41.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

600 μl of diphenylphosphoryl chloride and 510 μl of diisopropylethylamine were added dropwise, whilst ice-cooling, to a solution of 1000 mg of 4-nitrobenzyl (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 10 ml of dry acetonitrile, and the resulting mixture was stirred at the same temperature for 1 hour. 1800 μl of diisopropylethylamine and a solution of 1680 mg of (2S,4S)-4-mercapto-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-1-methylpyrrolidine bis(trifluoromethanesulfonate) (prepared as described in Preparation 52) in 5 ml of dry acetonitrile were then simultaneously added dropwise to the mixture, whilst ice-cooling, and the resulting mixture was stirred at the same temperature for 2 hours, after which it was allowed to stand overnight in a refrigerator. At the end of this time, the solvent was removed by distillation under reduced pressure, and the residue was subjected to column chromatography through a Lobar column (Merck, LiChroprep RP-8, size B). The column was eluted first with 55% v/v aqueous methanol and then with 60% v/v aqueous methanol. Those fractions containing the title compound were collected, concentrated by evaporation under reduced pressure and lyophilized, to give 710 mg of the title compound, as a powder.

Workup

  1. temperaturecooling
  2. stirringthe resulting mixture was stirred at the same temperature for 2 hours
  3. waitto stand overnight in a refrigerator
  4. customAt the end of this time, the solvent was removed by distillation under reduced pressure
  5. washThe column was eluted first with 55% v/v aqueous methanol
  6. additionThose fractions containing the title compound
  7. customwere collected
  8. concentrationconcentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-8c2f116a4ff14aabb43565881b85783b
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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