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

HRID 362012Notes

Reaction equation

HRID 362012 reaction equation
[Cl-].C(N(C(C)C)CC)(C)C.[OH:11][C@@H:12]([C@H:14]1[C:35](=[O:36])[N:16]2[CH:17]([C:22]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=3)=[O:23])[C:18](=O)[C@H:19]([CH3:20])[C@H:15]12)[CH3:13].FC(F)(F)S(O)(=O)=O.FC(F)(F)S(O)(=O)=O.[SH:53][C@@H:54]1[CH2:58][N:57]([CH3:59])[C@H:56]([C:60]([N:62]2[CH2:67][CH2:66][N:65]([CH3:68])[CH2:64][CH2:63]2)=[O:61])[CH2:55]1>C(#N)C>[CH3:68][N:65]1[CH2:66][CH2:67][N:62]([C:60]([C@@H:56]2[CH2:55][C@H:54]([S:53][C:18]3[C@H:19]([CH3:20])[C@@H:15]4[C@@H:14]([C@H:12]([OH:11])[CH3:13])[C:35](=[O:36])[N:16]4[C:17]=3[C:22]([O:24][CH2:25][C:26]3[CH:27]=[CH:28][C:29]([N+:32]([O-:34])=[O:33])=[CH:30][CH:31]=3)=[O:23])[CH2:58][N:57]2[CH3:59])=[O:61])[CH2:63][CH2:64]1

Participants

6

Reactant 4

HCID 312ChlorideHCID 81531Diisopropylethylamine2×HCID 98853021-Azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-, (4-nitrophenyl)methyl ester, (4R,5R,6S)-HCID 86752002(2S,4S)-4-Mercapto-2-(4-methyl-1-piperazinylcarbonyl)-1-methylpyrrolidine bis(trifluoromethanesulfonate)

Product 1

HCID 1317204284-Nitrobenzyl (1R,5S,6S)-2-[(2S,4S)-2-(4-methyl-1-piperazinylcarbonyl)-1-methylpyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylateYield 50%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

540 μl of diphenylphosophoryl chloride and 470 μl of diisopropylethylamine were added dropwise, whilst ice-cooling, to a solution of 920 mg of 4-nitro-benzyl (1R,5R,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. 1400 μl of diisopropylethylamine and a solution of 1350 mg of (2S,4S)-4-mercapto-2-(4-methyl-1-piperazinylcarbonyl)-1-methylpyrrolidine bis(trifluoromethanesulfonate) (prepared as described in Preparation 51) 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 purified by chromatography through a Lobar column (Merck, LiChroprep RP-8, size B). The column was successively eluted with 65% by volume aqueous methanol and with 70% by volume aqueous methanol. Those fractions containing the title compound were combined and concentrated by evaporation under reduced pressure, to give 730 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. customthe residue was purified by chromatography through a Lobar column (Merck, LiChroprep RP-8, size B)
  6. washThe column was successively eluted with 65% by volume aqueous methanol and with 70% by volume aqueous methanol
  7. additionThose fractions containing the title compound
  8. concentrationconcentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-51f24aaabba5428780ae36ca46f86f21
Source dataset
uspto-grants-1999_02
Patent number
US05866564

Reaction notes

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