HCID 131725339, compound → HCID 58595134, compound

HRID 891523Notes

Reaction equation

HRID 891523 reaction equation
[N+](C1C=CC(COC([NH:12][CH2:13][CH2:14][NH:15][C:16]([C:18]2[N:19]=[C:20]([N:23]3[CH2:26][CH:25]([S:27][C:28]4[C@H:29]([CH3:52])[C@@H:30]5[C@@H:47]([C@H:48]([OH:50])[CH3:49])[C:46](=[O:51])[N:31]5[C:32]=4[C:33]([O:35]CC4C=CC([N+]([O-])=O)=CC=4)=[O:34])[CH2:24]3)[S:21][CH:22]=2)=[O:17])=O)=CC=1)([O-])=O>O1CCCC1>[NH2:12][CH2:13][CH2:14][NH:15][C:16]([C:18]1[N:19]=[C:20]([N:23]2[CH2:24][CH:25]([S:27][C:28]3[C@H:29]([CH3:52])[C@@H:30]4[C@@H:47]([C@H:48]([OH:50])[CH3:49])[C:46](=[O:51])[N:31]4[C:32]=3[C:33]([OH:35])=[O:34])[CH2:26]2)[S:21][CH:22]=1)=[O:17]

Participants

3

Reactant 1

HCID 131725339HCID 131725339, compound

Product 1

HCID 58595134HCID 58595134, compoundYield 49.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

p-Nitrobenzyl (1R,5S,6S)-2-(1-{4-[(2-(p-nitrobenzyloxycarbonylamino)ethyl)carbamoyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (328.4 mg, 0.42 mmol) (obtained as described in Example 61(1)) in a mixture of tetrahydrofuran (16.4 ml) and distilled water (8.2 ml) was subjected to catalytic hydrogenation in the presence of 20% palladium hydroxide on charcoal (328.4 mg) in a water bath (30° C.) for 2 hours. After checking the completion of the reaction, the reaction mixture was filtered and to the filtrate were added ethyl acetate-tetrahydrofuran (1:1) and distilled water. The mixture was shaken in a separatory funnel. The aqueous layer was separated, washed with the above-mentioned mixed solvent, and concentrated under reduced pressure. The residue was purified by chromatography on a Cosmosil column (eluant: distilled water→5% acetonitrile in distilled water→10% acetonitrile in distilled water→15% acetonitrile in distilled water) and the eluate was lyophilized to afford the desired compound (1R,5S,6S)-2-{1-[4-((2-aminoethyl)carbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid (96.4 mg, yield 49%) as a white solid.

Workup

  1. distillationdistilled water (8.2 ml)
  2. customwas subjected to catalytic hydrogenation in the presence of 20% palladium hydroxide on charcoal (328.4 mg) in a water bath
  3. customthe completion of the reaction
  4. filtrationthe reaction mixture was filtered and to the filtrate
  5. additionwere added ethyl acetate-tetrahydrofuran (1:1)
  6. distillationdistilled water
  7. customThe aqueous layer was separated
  8. washwashed with the above-mentioned mixed solvent
  9. concentrationconcentrated under reduced pressure
  10. distillationThe residue was purified by chromatography on a Cosmosil column (eluant: distilled water→5% acetonitrile in distilled water→10% acetonitrile in distilled water→15% acetonitrile in distilled water)

Sources & evidence

ORD record
ord-0b2ed772cb804ff6b13846f5fcdf978b
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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