Carbon Dioxide → Ertapenem disodium

HRID 2067711Notes

Reaction equation

HRID 2067711 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>O.C(=O)(O)O.C1COCC1.CN(C=O)C.C(OCC)(=O)C.[Pd].[C]>[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

10

Reactant 4

HCID 280Carbon DioxideHCID 150610ErtapenemHCID 516892Sodium BicarbonateHCID 5360545Sodium

Product 1

HCID 150611Ertapenem disodium

Reagents, catalysts & solvents 5

HCID 178418390HCID 178418390, compoundCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 21993411Carbonic acid--water (1/1)Solvent

Procedure

To the solution of sodium salt of di-protected Ertapenem (IV) (50 g) in carbonic acid water (500 ml), THF (100 ml), DMF (25 ml) and ethyl acetate (1000 mL) and sodium bicarbonate (6.5 gm) in autoclave, Pd/carbon charged and subjected to hydrogenation with 8 to 10 Kg pressure at 5-10° C. After completion of reaction CO2 gas was purged, the reaction mass was filtered. The aqueous layer was separated, washed with ethyl acetate and the residual solvents in aqueous layer removed using degassing technique. The aqueous layer was added in to isopropyl alcohol (12 L) under stirring. The precipitated Ertapenem disodium was filtered, washed with IPA and dried to yield amorphous form of Ertapenem disodium of formula (I). The solid obtained was optionally treated with methanol/isopropyl ether mixture at about −20° C. to yield Ertapenem disodium with low residual solvent content.

Workup

  1. customsubjected to hydrogenation with 8 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. customthe residual solvents in aqueous layer removed
  7. customusing degassing technique
  8. additionThe aqueous layer was added in to isopropyl alcohol (12 L)
  9. filtrationThe precipitated Ertapenem disodium was filtered
  10. washwashed with IPA
  11. customdried

Sources & evidence

ORD record
ord-56fbccdb14254990bf8545fddae3939e
Source dataset
uspto-grants-2012_10
Patent number
US08293894B2

Reaction notes

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