(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 → (1R,5S,6S)-2-[(2S,4S)-2-(4-Amidinopiperazin-1-ylcarbonyl)-1-methylpyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid

HRID 727700Notes

Reaction equation

HRID 727700 reaction equation
[OH:1][C@@H:2]([C@H:4]1[C:55](=[O:56])[N:6]2[C:7]([C:42]([O:44]CC3C=CC([N+]([O-])=O)=CC=3)=[O:43])=[C:8]([S:11][C@@H:12]3[CH2:16][N:15]([CH3:17])[C@H:14]([C:18]([N:20]4[CH2:25][CH2:24][N:23]([C:26](=[NH:41])[NH:27]C(OCC5C=CC([N+]([O-])=O)=CC=5)=O)[CH2:22][CH2:21]4)=[O:19])[CH2:13]3)[C@H:9]([CH3:10])[C@H:5]12)[CH3:3].[H][H]>O1CCCC1.O.[Pd]>[C:26]([N:23]1[CH2:24][CH2:25][N:20]([C:18]([C@@H:14]2[CH2:13][C@H:12]([S:11][C:8]3[C@H:9]([CH3:10])[C@@H:5]4[C@@H:4]([C@H:2]([OH:1])[CH3:3])[C:55](=[O:56])[N:6]4[C:7]=3[C:42]([OH:44])=[O:43])[CH2:16][N:15]2[CH3:17])=[O:19])[CH2:21][CH2:22]1)(=[NH:27])[NH2:41]

Participants

6

Reactant 2

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-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 22881596(1R,5S,6S)-2-[(2S,4S)-2-(4-Amidinopiperazin-1-ylcarbonyl)-1-methylpyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

500 ml of 4-nitrobenzyl (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-{(2S,4S) -1-methyl-2-[4-(4-nitrobenzyloxycarbonylamidino)piperazin-1-ylcarbonyl]-pyrrolidin-4-yl-thio}-1-carbapen-2-em-3-carboxylate [prepared as described in step (1) above] were dissolved in 75 ml of a 1:1 by volume mixture of tetrahydrofuran and water, and 2400 mg of a 10% w/w palladium-on-carbon catalyst were added to the resulting solution. The mixture was then hydrogenated in an atmosphere of hydrogen at 28° C. for 1 hour. At the end of this time, the catalyst was removed by filtration, and the filtrate was washed with diethyl ether. The filtrate was then concentrated to 20 ml by evaporation under reduced pressure. The solution was then subjected to reverse phase silica gel column chromatography (Cosmosil 75C18 -prep, manufactured by Nacalai Tesque, 100 ml), eluted with mixtures of acetonitrile and water in proportions of 0:100, 2:98, 4:96, 6:94 and 8:92 by volume, in that order. The fractions containing the desired compound were collected, concentrated to 3 ml by evaporation under reduced pressure, and cooled to precipitate colorless needle-like crystals. The crystals were filtered off and dried to obtain 435 mg of the title compound as crystals, melting at 218°-220° C. (with decomposition).

Workup

  1. additionwere added to the resulting solution
  2. customAt the end of this time, the catalyst was removed by filtration
  3. washthe filtrate was washed with diethyl ether
  4. concentrationThe filtrate was then concentrated to 20 ml by evaporation under reduced pressure
  5. washeluted with mixtures of acetonitrile and water in proportions of 0:100, 2:98, 4:96, 6:94 and 8:92 by volume, in that order
  6. additionThe fractions containing the desired compound
  7. customwere collected
  8. concentrationconcentrated to 3 ml by evaporation under reduced pressure
  9. temperaturecooled
  10. customto precipitate colorless needle-like crystals
  11. filtrationThe crystals were filtered off
  12. customdried

Sources & evidence

ORD record
ord-b5f2ff3e5bc1405c96f0e04fc4fe3cc0
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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