Diethyl Ether → (1R,5S,6S)-2-[2-(3-Oxopiperazin-1-yl)-2-iminoethylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid

HRID 622437Notes

Reaction equation

HRID 622437 reaction equation
Cl.[O:2]=[C:3]1[NH:8][CH2:7][CH2:6][N:5]([C:9](=[NH:12])[CH2:10][SH:11])[CH2:4]1.C1(S([C:21]2[CH:22]([CH3:45])[C@@H:23]3[C@@H:40]([C@H:41]([OH:43])[CH3:42])[C:39](=[O:44])[N:24]3[C:25]=2[C:26]([O:28]CC2C=CC([N+]([O-])=O)=CC=2)=[O:27])=O)C=CC=CC=1.C(OCC)C>CS(C)=O.C(#N)C>[O:2]=[C:3]1[NH:8][CH2:7][CH2:6][N:5]([C:9](=[NH:12])[CH2:10][S:11][C:21]2[C@H:22]([CH3:45])[C@@H:23]3[C@@H:40]([C@H:41]([OH:43])[CH3:42])[C:39](=[O:44])[N:24]3[C:25]=2[C:26]([OH:28])=[O:27])[CH2:4]1

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 212929952-(3-Oxopiperazin-1-yl)-2-iminoethylmercaptan hydrochlorideHCID 22839820p-Nitrobenzyl(1RS,5S,6S)-2-phenylsulfinyl-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

Product 1

HCID 22839793(1R,5S,6S)-2-[2-(3-Oxopiperazin-1-yl)-2-iminoethylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6342AcetonitrileSolvent

Procedure

A suspension of 108 mg of 2-(3-oxopiperazin-1-yl)-2-iminoethylmercaptan hydrochloride in 0.8 ml of dimethyl sulfoxide was added, under ice-cooling, to a solution of 130 mg of p-nitrobenzyl (1RS,5S,6S)-2-phenylsulfinyl-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate in 1.4 ml of acetonitrile, and the mixture was stirred for 30 minutes. The reaction mixture was then poured into 50 ml of anhydrous diethyl ether, and the solvent was decanted off. The oily residue was dissolved in a mixture of 8 ml of tetrahydrofuran, 2.7 ml of water and 9.4 ml of 0.1M phosphate buffer solution (pH 7.0), and the resulting solution was subjected to catalytic hydrogenation at room temperature for 2 hours in the presence of 160 mg of palladium-carbon. The insolubles were filtered off over "Celite" (Trade Mark) filter aid, and the filtrate was extracted twice with 30 ml portions of diethyl ether. The aqueous phase was concentrated by evaporation under reduced pressure and the residue was purified through a Lobar column (Merck "LiChloprep RP-8", size B, two columns), eluted with 5% aqueous methanol, to give the title compound having the same properties as those of the product obtained in Example 13.

Workup

  1. additionwas added, under ice-
  2. customthe solvent was decanted off
  3. dissolutionThe oily residue was dissolved in a mixture of 8 ml of tetrahydrofuran, 2.7 ml of water and 9.4 ml of 0.1M phosphate buffer solution (pH 7.0)
  4. waitthe resulting solution was subjected to catalytic hydrogenation at room temperature for 2 hours in the presence of 160 mg of palladium-carbon
  5. filtrationThe insolubles were filtered off over "Celite" (Trade Mark)
  6. filtrationfilter aid
  7. extractionthe filtrate was extracted twice with 30 ml portions of diethyl ether
  8. concentrationThe aqueous phase was concentrated by evaporation under reduced pressure
  9. customthe residue was purified through a Lobar column (Merck "LiChloprep RP-8", size B, two columns)
  10. washeluted with 5% aqueous methanol

Sources & evidence

ORD record
ord-eb01e110f5fe467fbf438b21a0ee319c
Source dataset
uspto-grants-1988_09
Patent number
US04771046

Reaction notes

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