p-nitrobenzyl (1R,5R,6S)-2-(di-phenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylate → (4-nitrophenyl)methyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[(3S,5S)-1-methyl-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 727699Notes

Reaction equation

HRID 727699 reaction equation
C1(P(O[C:16]2[C@H:17]([CH3:40])[C@@H:18]3[C@@H:35]([C@H:36]([OH:38])[CH3:37])[C:34](=[O:39])[N:19]3[C:20]=2[C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=2)=[O:22])(C2C=CC=CC=2)=O)C=CC=CC=1.[SH:41][C@@H:42]1[CH2:46][N:45]([CH3:47])[C@H:44]([C:48]([N:50]2[CH2:55][CH2:54][N:53]([C:56](=[NH:71])[NH:57][C:58]([O:60][CH2:61][C:62]3[CH:67]=[CH:66][C:65]([N+:68]([O-:70])=[O:69])=[CH:64][CH:63]=3)=[O:59])[CH2:52][CH2:51]2)=[O:49])[CH2:43]1>C(#N)C.C(N(C(C)C)CC)(C)C>[OH:38][C@@H:36]([C@H:35]1[C:34](=[O:39])[N:19]2[C:20]([C:21]([O:23][CH2:24][C:25]3[CH:26]=[CH:27][C:28]([N+:31]([O-:33])=[O:32])=[CH:29][CH:30]=3)=[O:22])=[C:16]([S:41][C@@H:42]3[CH2:46][N:45]([CH3:47])[C@H:44]([C:48]([N:50]4[CH2:55][CH2:54][N:53]([C:56](=[NH:71])[NH:57][C:58]([O:60][CH2:61][C:62]5[CH:67]=[CH:66][C:65]([N+:68]([O-:70])=[O:69])=[CH:64][CH:63]=5)=[O:59])[CH2:52][CH2:51]4)=[O:49])[CH2:43]3)[C@H:17]([CH3:40])[C@H:18]12)[CH3:37]

Participants

5

Reactant 2

HCID 15871605p-nitrobenzyl (1R,5R,6S)-2-(di-phenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylateHCID 140386407(4-nitrophenyl)methyl N-[4-[(2S,4S)-1-methyl-4-sulfanylpyrrolidine-2-carbonyl]piperazine-1-carboximidoyl]carbamate

Product 1

HCID 141580151(4-nitrophenyl)methyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[(3S,5S)-1-methyl-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 76.9%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 81531DiisopropylethylamineSolvent

Procedure

1600 mg of 4-nitrobenzyl (1R, 5R,6S)-2-(diphenylphosphoryloxy)-6-[(1R) -1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate (prepared as described in Preparation 123) were dissolved in 16 ml of dry acetonitrile, and a solution of 1120 mg of (2S,4S)-4-mercapto-1-methyl-2-[4-(4-nitrobenzyloxycarbonylamidino) piperazin-1-ylcarbonyl]pyrrolidine (prepared as described in Preparation 93) in 11 ml of dry acetonitrile and 430 μl of diisopropylethylamine were added dropwise to the resulting solution, whilst ice-cooling. The resulting mixture was stirred at the same temperature overnight, after which it was concentrated by evaporation under reduced pressure. The resulting residue was diluted with ethyl acetate, and the mixture was washed with an aqueous solution of sodium hydrogencarbonate, with water and with an aqueous solution of sodium chloride, in that order. The ethyl acetate layer was dehydrated over anhydrous sodium sulfate and then concentrated by evaporation under reduced pressure. The resulting residue was subjected to reverse phase silica gel column chromatography (Cosmosil 75C18 -prep, manufactured by Nacalai Tesque, 300 ml), eluted with a 1 by volume mixture of acetonitrile and water. The fractions containing the desired compound were collected and concentrated by evaporation under reduced pressure, to obtain 1520 mg of the title compound, as a powder.

Workup

  1. temperaturecooling
  2. concentrationafter which it was concentrated by evaporation under reduced pressure
  3. additionThe resulting residue was diluted with ethyl acetate
  4. washthe mixture was washed with an aqueous solution of sodium hydrogencarbonate, with water and with an aqueous solution of sodium chloride, in that order
  5. concentrationconcentrated by evaporation under reduced pressure
  6. washeluted with a 1 by volume mixture of acetonitrile and water
  7. additionThe fractions containing the desired compound
  8. customwere collected
  9. concentrationconcentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-dceac836067d42b2961e5334193044a2
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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