HCID 131725340, compound → HCID 58595192, compound

HRID 891524Notes

Reaction equation

HRID 891524 reaction equation
[CH3:1][N:2]([CH2:40][CH2:41][NH:42]C(OCC1C=CC([N+]([O-])=O)=CC=1)=O)[C:3]([C:5]1[N:6]=[C:7]([N:10]2[CH2:13][CH:12]([S:14][C:15]3[C@H:16]([CH3:39])[C@@H:17]4[C@@H:34]([C@H:35]([OH:37])[CH3:36])[C:33](=[O:38])[N:18]4[C:19]=3[C:20]([O:22]CC3C=CC([N+]([O-])=O)=CC=3)=[O:21])[CH2:11]2)[S:8][CH:9]=1)=[O:4]>O1CCCC1>[NH2:42][CH2:41][CH2:40][N:2]([CH3:1])[C:3]([C:5]1[N:6]=[C:7]([N:10]2[CH2:11][CH:12]([S:14][C:15]3[C@H:16]([CH3:39])[C@@H:17]4[C@@H:34]([C@H:35]([OH:37])[CH3:36])[C:33](=[O:38])[N:18]4[C:19]=3[C:20]([OH:22])=[O:21])[CH2:13]2)[S:8][CH:9]=1)=[O:4]

Participants

3

Reactant 1

HCID 131725340HCID 131725340, compound

Product 1

HCID 58595192HCID 58595192, compoundYield 51.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

p-Nitrobenzyl (1R,5S,6S)-2-[1-(4-{N-methyl-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 (267.5 mg, 0.33 mmol) (obtained as described in Example 63(1)) in a mixture of tetrahydrofuran (14 ml) and distilled water (6.7 ml) was subjected to catalytic hydrogenation in the presence of 20% palladium hydroxide on charcoal (300 mg) at 30° C. in a water bath for 1.5 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-[N-(2-aminoethyl)-N-methyl-carbamoyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid (81.6 mg, yield 51%) as a white solid.

Workup

  1. distillationdistilled water (6.7 ml)
  2. customthe completion of the reaction
  3. filtrationthe reaction mixture was filtered and to the filtrate
  4. additionwere added ethyl acetate-tetrahydrofuran (1:1)
  5. distillationdistilled water
  6. customThe aqueous layer was separated
  7. washwashed with the above-mentioned mixed solvent
  8. concentrationconcentrated under reduced pressure
  9. 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-5c3d3b4c3d164518a8df493cbb2bb579
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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