HCID 131725352, compound → HCID 131725350, compound

HRID 891534Notes

Reaction equation

HRID 891534 reaction equation
[N+](C1C=CC([CH2:8][C@:9]2(C)[C@@H:13]3[C@@H:14]([C@H:17]([OH:19])[CH3:18])[C:15](=[O:16])[N:12]3[C:11]([C:20]([O-:22])=[O:21])=[C:10]2[S:23][CH:24]2[CH2:27][N:26]([C:28]3[S:29][CH:30]=[C:31]([CH2:33][NH:34][C:35]([C:37]4[O:38][CH:39]=[CH:40][CH:41]=4)=[O:36])[N:32]=3)[CH2:25]2)=CC=1)([O-])=O.[Na+:45].O1C=CC=C1C(NCC1N=C(N2CC(SC3[C@H](C)[C@@H]4[C@@H]([C@H](O)C)C(=O)N4C=3C(O)=O)C2)SC=1)=O>O1CCCC1>[Na+:45].[O:38]1[CH:39]=[CH:40][CH:41]=[C:37]1[C:35]([NH:34][CH2:33][C:31]1[N:32]=[C:28]([N:26]2[CH2:27][CH:24]([S:23][C:10]3[C@H:9]([CH3:8])[C@@H:13]4[C@@H:14]([C@H:17]([OH:19])[CH3:18])[C:15](=[O:16])[N:12]4[C:11]=3[C:20]([O-:22])=[O:21])[CH2:25]2)[S:29][CH:30]=1)=[O:36]

Participants

3

Reactant 1

HCID 131725352HCID 131725352, compound

Product 1

HCID 131725350HCID 131725350, compoundYield 41.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(1R,5S,6S)-2-(1-{4-[(furan-2-carbonylamino)methyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid sodium salt p-Nitrobenzyl (1R,5S,6S)-2-(1-{4-[(furan-2-carbonylamino)methyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (640 mg,1.00 mmol) (obtained as described in Example 72(1)) in a mixture of tetrahydrofuran (32 ml) and distilled water (32 ml) was subjected to catalytic hydrogenation in the presence of 7.5% palladium on charcoal (640 mg) in a water bath (35° C.) for 2 hours. After checking the completion of the reaction, the reaction mixture was filtered and to the filtrate were added sodium hydrogencarbonate (84 mg), ethyl acetate and distilled water. 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→15% acetonitrile in distilled water) and the eluate was lyophilized to afford the desired compound (1R,5S,6S)-2-(1-{4-[(furan-2-carbonylamino)methyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid sodium salt (218 mg, yield 41%) as a white solid.

Workup

  1. distillationdistilled water (32 ml)
  2. customwas subjected to catalytic hydrogenation in the presence of 7.5% palladium on charcoal (640 mg) in a water bath
  3. customthe completion of the reaction
  4. filtrationthe reaction mixture was filtered and to the filtrate
  5. additionwere added sodium hydrogencarbonate (84 mg), ethyl acetate
  6. distillationdistilled water
  7. customthe aqueous layer was separated
  8. concentrationconcentrated under reduced pressure
  9. 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→15% acetonitrile in distilled water)

Sources & evidence

ORD record
ord-63a0e18421ca42c9b83350e3dae06190
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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