Sulfuric Acid → Sodium (5R,6S)-2-acetamido-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate

HRID 329679Notes

Reaction equation

HRID 329679 reaction equation
[NH2:1][C:2]1[CH2:3][C@@H:4]2[C@@H:11]([C@H:12]([OH:14])[CH3:13])[C:10](=[O:15])[N:5]2[C:6]=1[C:7]([O-:9])=[O:8].[Na+:16].C(=O)(O)[O-].[Na+].[C:22](Cl)(=[O:24])[CH3:23].S(=O)(=O)(O)O>O.O1CCOCC1>[C:22]([NH:1][C:2]1[CH2:3][C@@H:4]2[C@@H:11]([C@H:12]([OH:14])[CH3:13])[C:10](=[O:15])[N:5]2[C:6]=1[C:7]([O-:9])=[O:8])(=[O:24])[CH3:23].[Na+:16]

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 6367Acetyl chlorideHCID 516892Sodium BicarbonateHCID 23718245sodium (5R,6S)-2-amino-6-[(R)-1-hydoxyethyl]carbapen-2-em-3-carboxylate

Product 1

HCID 23718247Sodium (5R,6S)-2-acetamido-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A solution of sodium (5R,6S)-2-amino-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate (23 mg, 0.1 mmol) in water (2.5 ml) is cooled in an ice-bath, stirred, and treated with sodium bicarbonate (84 mg, 1 mmol) and dioxane. The resulting solution is stirred in the cold while a solution of acetyl chloride (11 μl, 0.15 mmol) in dioxane (0.5 ml) is added dropwise over 10 minutes. After stirring an additional 30 minutes, the solution is acidified to pH 6.8 with 1M sulfuric acid and extracted with diethyl ether (3×10 ml). The aqueous phase is layered with ethyl acetate (2.5 ml) and vigorously stirred in an ice-bath while acidifying to pH 2.3 with 1M sulfuric acid. The aqueous phase is separated and extracted with more ethyl acetate (2×2 ml). The combined ethyl acetate solution is washed with brine, then layered with water (5 ml) and stirred vigorously in an ice-bath while the pH is brought to 7 with 1N sodium hydroxide. The aqueous phase is separated, concentrated under vacuum, and lyophilized to yield sodium (5R,6S)-2-acetamido-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate (32).

Workup

  1. additionis added dropwise over 10 minutes
  2. stirringAfter stirring an additional 30 minutes
  3. extractionextracted with diethyl ether (3×10 ml)
  4. stirringvigorously stirred in an ice-bath
  5. customThe aqueous phase is separated
  6. extractionextracted with more ethyl acetate (2×2 ml)
  7. washThe combined ethyl acetate solution is washed with brine
  8. stirringstirred vigorously in an ice-bath while the pH
  9. customThe aqueous phase is separated
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-04892f57518f407f8642cad83a994ffd
Source dataset
uspto-grants-1990_01
Patent number
US04892869

Reaction notes

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