Carbon Dioxide → Ertapenem disodium

HRID 2068129Notes

Reaction equation

HRID 2068129 reaction equation
[Na].[CH3:2][C@H:3]1[C:10]([S:11][C@@H:12]2[CH2:16][NH:15][C@H:14]([C:17]([NH:19][C:20]3[CH:21]=[CH:22][CH:23]=[C:24]([C:26]([OH:28])=[O:27])[CH:25]=3)=[O:18])[CH2:13]2)=[C:9]([C:29]([OH:31])=[O:30])[N:8]2[C@H:4]1[C@@H:5]([C@H:32]([OH:34])[CH3:33])[C:6]2=[O:7].C(=O)(O)[O-].[Na+:39].C(=O)=O>[Pd].[C].C(OCC)(=O)C.CC(O)C.O>[CH3:2][C@H:3]1[C:10]([S:11][C@@H:12]2[CH2:16][NH:15][C@H:14]([C:17]([NH:19][C:20]3[CH:25]=[C:24]([C:26]([O-:28])=[O:27])[CH:23]=[CH:22][CH:21]=3)=[O:18])[CH2:13]2)=[C:9]([C:29]([O-:31])=[O:30])[N:8]2[C@H:4]1[C@@H:5]([C@H:32]([OH:34])[CH3:33])[C:6]2=[O:7].[Na+:39].[Na+:39]

Participants

9

Reactant 4

HCID 280Carbon DioxideHCID 150610ErtapenemHCID 516892Sodium BicarbonateHCID 5360545Sodium

Product 1

HCID 150611Ertapenem disodiumYield 7%

Reagents, catalysts & solvents 4

HCID 178418390HCID 178418390, compoundCatalystHCID 962WaterSolventHCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the solution of sodium salt of di-protected Ertapenem (50 g) {prepared by following the process disclosed in WO 2008062279} in a mixture of carbonated water (500 ml), IPA (2.6 ml) and ethyl acetate (20 L) in autoclave were charged sodium bicarbonate (6.5 gm) and Pd/carbon and subjected to hydrogenation with 3 to 10 Kg pressure at 5-10° C. After completion of reaction CO2 gas was purged and the reaction mass was filtered. The aqueous layer was separated, washed with ethyl acetate and was treated with activated carbon and neutral alumina, the residual solvents in aqueous layer removed using degassing technique and filtered. The aqueous layer was filtered through 0.2 micron filter paper and added into isopropyl alcohol and ethanol under stirring. The precipitated amorphous form of Ertapenem disodium (having moisture content: about 7% to 11%) was slurry washed with ethanol and IPE. The obtained solid (having moisture content: about 2.5% to 6%) was dried using dry N2 gas followed by humidified N2 gas to yield amorphous form of Ertapenem disodium (having moisture content: about 7% to 12%) and again dried using dry N2 gas at about 5-10° C. to yield amorphous form of Ertapenem disodium having moisture content (2.5-4.5%) with pharmaceutically acceptable level of residual solvent.

Workup

  1. customsubjected to hydrogenation with 3 to 10 Kg pressure at 5-10° C
  2. customwas purged
  3. filtrationthe reaction mass was filtered
  4. customThe aqueous layer was separated
  5. washwashed with ethyl acetate
  6. additionwas treated with activated carbon and neutral alumina
  7. customthe residual solvents in aqueous layer removed
  8. customusing degassing technique
  9. filtrationfiltered
  10. filtrationThe aqueous layer was filtered through 0.2 micron
  11. filtrationfilter paper
  12. additionadded into isopropyl alcohol and ethanol
  13. washwashed with ethanol and IPE
  14. customThe obtained solid (having moisture content: about 2.5% to 6%) was dried

Sources & evidence

ORD record
ord-fc2dd242e879490c9b6a00f616add88d
Source dataset
uspto-grants-2012_10
Patent number
US08293924B2

Reaction notes

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