HCID 131725343, compound → HCID 58595118, compound

HRID 891527Notes

Reaction equation

HRID 891527 reaction equation
[CH:1]([N:4]([CH2:42][CH2:43][NH:44]C(OCC1C=CC([N+]([O-])=O)=CC=1)=O)[C:5]([C:7]1[N:8]=[C:9]([N:12]2[CH2:15][CH:14]([S:16][C:17]3[C@H:18]([CH3:41])[C@@H:19]4[C@@H:36]([C@H:37]([OH:39])[CH3:38])[C:35](=[O:40])[N:20]4[C:21]=3[C:22]([O:24]CC3C=CC([N+]([O-])=O)=CC=3)=[O:23])[CH2:13]2)[S:10][CH:11]=1)=[O:6])([CH3:3])[CH3:2]>O1CCCC1>[NH2:44][CH2:43][CH2:42][N:4]([CH:1]([CH3:3])[CH3:2])[C:5]([C:7]1[N:8]=[C:9]([N:12]2[CH2:13][CH:14]([S:16][C:17]3[C@H:18]([CH3:41])[C@@H:19]4[C@@H:36]([C@H:37]([OH:39])[CH3:38])[C:35](=[O:40])[N:20]4[C:21]=3[C:22]([OH:24])=[O:23])[CH2:15]2)[S:10][CH:11]=1)=[O:6]

Participants

3

Reactant 1

HCID 131725343HCID 131725343, compound

Product 1

HCID 58595118HCID 58595118, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

p-Nitrobenzyl (1R,5S,6S)-2-[1-(4-{N-isopropyl-N-[2-(p-nitrobenzyloxycarbonylamino)ethyl]-carbamoyl}-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (610 mg, 0.74 mmol) (obtained as described in Example 65(1)) in a mixture of tetrahydrofuran (30 ml) and distilled water (30 ml) was subjected to catalytic hydrogenation in the presence of 7.5% palladium on charcoal (610 mg) in a water bath (35° C.) for 2 hours. After checking the completion of the reaction, ethyl acetate and distilled water were added to the reaction mixture. The resulting mixture was shaken in a separatory funnel and the aqueous layer was separated and concentrated under reduced pressure. The residue was purified by chromatography on a Cosmosil column (eluant: distilled water→2% acetonitrile in distilled water→4% acetonitrile in distilled water→6% acetonitrile in distilled water→8% acetonitrile in distilled water→10% acetonitrile in distilled water→12% acetonitrile in distilled water→14% acetonitrile in distilled water→16% acetonitrile in distilled water→18% acetonitrile in distilled water) and the eluate was lyophilized to afford the desired compound (1R,5S,6S)-2-(1-{4-[N-(2-aminoethyl)-N-isopropyl-carbamoyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid (104 mg, yield 28%) as a white solid.

Workup

  1. distillationdistilled water (30 ml)
  2. customwas subjected to catalytic hydrogenation in the presence of 7.5% palladium on charcoal (610 mg) in a water bath
  3. customthe completion of the reaction, ethyl acetate
  4. distillationdistilled water
  5. additionwere added to the reaction mixture
  6. customthe aqueous layer was separated
  7. concentrationconcentrated under reduced pressure
  8. distillationThe residue was purified by chromatography on a Cosmosil column (eluant: distilled water→2% acetonitrile in distilled water→4% acetonitrile in distilled water→6% acetonitrile in distilled water→8% acetonitrile in distilled water→10% acetonitrile in distilled water→12% acetonitrile in distilled water→14% acetonitrile in distilled water→16% acetonitrile in distilled water→18% acetonitrile in distilled water)

Sources & evidence

ORD record
ord-e328ea2ae2d84b5ca204294169bab5ed
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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