Phosphate → Meropenem Trihydrate

HRID 420872Notes

Reaction equation

HRID 420872 reaction equation
[CH3:1][C@H:2]1[C:9]([S:10][C@@H:11]2[CH2:15][NH:14][C@H:13]([C:16]([N:18]([CH3:20])[CH3:19])=[O:17])[CH2:12]2)=[C:8]([C:21]([OH:23])=[O:22])[N:7]2[C@H:3]1[C@@H:4]([C@H:24]([OH:26])[CH3:25])[C:5]2=[O:6].P([O-])([O-])([O-])=[O:28].N1CC[O:35]CC1>[Pd].O1CCCC1.O.C(=O)(O)O>[CH3:1][C@H:2]1[C:9]([S:10][C@@H:11]2[CH2:15][NH:14][C@H:13]([C:16]([N:18]([CH3:19])[CH3:20])=[O:17])[CH2:12]2)=[C:8]([C:21]([OH:23])=[O:22])[N:7]2[C@H:3]1[C@@H:4]([C@H:24]([OH:26])[CH3:25])[C:5]2=[O:6].[OH2:28].[OH2:35].[OH2:6]

Participants

7

Reactant 3

HCID 1061PhosphateHCID 8083MorpholineHCID 441130Meropenem2×

Product 1

HCID 441129Meropenem Trihydrate

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolventHCID 21993411Carbonic acid--water (1/1)Solvent

Procedure

The process described as above is used to manufacture proteceted meropenem in crystalline form with desirable yield in about 90-95% and with a purity above 99%. Furthermore, protected meropenem is treated with palladium on charcoal (Pd/C) in a mixture of tetrahydrofuran and carbonate water or phosphate buffer or morpholine buffer of pH-7 so as to retain reaction mass pH 6.5 to 6.9 at temperature of 30-35° C. for 2- 3 hours to achieve a maximum yield. After completion of the reaction, the reaction mass is degasified and charcoalised to form a clear aqueous layer which is further reduced by distillation and finally acetone is added at a maintained temperature of 0-5° C. for 3 hours to get crystalline meropenem trihydrate in pure form.

Workup

  1. customwith desirable yield in about 90-95% and with a purity above 99%
  2. customreaction mass pH 6.5 to 6.9 at temperature of 30-35° C. for 2- 3 hours
  3. customAfter completion of the reaction
  4. customto form a clear aqueous layer which
  5. distillationis further reduced by distillation and finally acetone
  6. additionis added at a maintained temperature of 0-5° C. for 3 hours

Sources & evidence

ORD record
ord-fe46088f9e8a4fdcb227dd28936dc964
Source dataset
uspto-grants-2012_01
Patent number
US08097719B2

Reaction notes

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