Meropenem → Meropenem Trihydrate

HRID 589655Notes

Reaction equation

HRID 589655 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].[OH:27]P([O-])(O)=O.[K+]>O1CCCC1.O.[Zn]>[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].[OH2:27].[OH2:6].[OH2:6]

Participants

6

Reactant 2

HCID 441130MeropenemHCID 516951Monobasic potassium phosphate

Product 1

HCID 441129Meropenem TrihydrateYield 133.4%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalyst2×HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
27 °C

Procedure

20 g of meropenem-PNB was dissolved in 200 mL of tetrahydrofuran. 60 g of potassium phosphate monobasic (KH2PO4) dissolved in 400 mL of water was added thereto and heated to 27° C. 80 g of zinc powder was slowly added portionwise and stirred between 25 and 35° C. for 1 hour. After completion of the reaction, zinc powder was removed by filtration. 220 mL of methylene chloride was added and stirred, and the phases were separated. The aqueous layer was isolated and washed 2 times with 100 mL of methylene chloride, by which tetrahydrofuran present in the aqueous layer was removed completely. After the aqueous layer was cooled, 800 mL of cooled methanol was added dropwise to precipitate potassium phosphate crystal. After the crystal was filtered, the filtrate was passed through a column filled with rinsed cationic resin BCMB50 to remove the remaining phosphate. A buffer solution of N-methylmorpholine/acetic acid (pH 6.5) was added thereto, and concentration was conducted to a volume 10 times greater than the weight of meropenem-PNB. 1100 mL of acetone was added to generate crystal and stirred at room temperature for 1 hour. After filtration and drying, 10.15 g of meropenem trihydrate was obtained.

Workup

  1. additionwas added
  2. customwas removed by filtration
  3. addition220 mL of methylene chloride was added
  4. stirringstirred
  5. customthe phases were separated
  6. customThe aqueous layer was isolated
  7. washwashed 2 times with 100 mL of methylene chloride
  8. customby which tetrahydrofuran present in the aqueous layer was removed completely
  9. temperatureAfter the aqueous layer was cooled
  10. addition800 mL of cooled methanol was added dropwise
  11. customto precipitate potassium phosphate crystal
  12. filtrationAfter the crystal was filtered
  13. additionfilled
  14. washwith rinsed cationic resin
  15. customto remove the remaining phosphate
  16. additionA buffer solution of N-methylmorpholine/acetic acid (pH 6.5) was added
  17. concentrationconcentration
  18. addition1100 mL of acetone was added
  19. stirringstirred at room temperature for 1 hour
  20. filtrationAfter filtration
  21. customdrying

Sources & evidence

ORD record
ord-63abcde554fd4443a1847fe973c65333
Source dataset
uspto-grants-2016_01
Patent number
US09233963B2

Reaction notes

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