Triethylamine → (6R)-8-Oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 839458

Reaction equation

HRID 839458 reaction equation
C(N(CC)CC)C.C(Cl)(=O)C(Cl)=O.C(OC[C:19]1[CH2:20][S:21][C@@H:22]2[C@H:29](N)[C:28](=[O:31])[N:23]2[C:24]=1[C:25]([OH:27])=[O:26])(=O)C.C(=O)([O-])O.[Na+]>C(Cl)Cl.CN(C)C=O.O.CC(C)=O>[S:21]1[C@@H:22]2[CH2:29][C:28](=[O:31])[N:23]2[C:24]([C:25]([OH:27])=[O:26])=[CH:19][CH2:20]1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 4413287-Aminocephalosporanic acidHCID 516892Sodium Bicarbonate

Product 1

HCID 52921562(6R)-8-Oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 180AcetoneSolvent2×HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Following the procedure described in Example 1, a solution of the appropriate 2-aryl-2-t-butoxycarbonyl-Rq -oxyiminoacetic acid (syn-isomer) (1 equiv) in methylene chloride optionally containing a few drops of N,N-dimethylformamide and triethylamine (1 equiv) was treated with oxalyl chloride (1 equiv) at 0°-5° for ca. 1 hour. The mixture was then evaporated to dryness. The residue was suspended or dissolved in acetone and added to a stirred, ice-cold solution of (6R,7R)-3-acetoxymethyl-7-aminoceph-3-em-4-carboxylic acid (1-1.2 equiv) in water or a mixture of acetone and water containing sodium hydrogen carbonate (2-2.5 equiv). The reaction mixture was stirred for 0.5-2.5 hours, allowing the temperature to rise to room temperature, whereafter the acetone was removed under reduced pressure. The pH was adjusted to 1.5- 2.0 and the product extracted into ethyl acetate (alternatively ether or methylene chloride may be used). The organic layer was washed with water and/or saturated brine, dried and evaporated to give the corresponding (6R,7R)-3-acetoxymethyl-7-(2-aryl-2-t-butoxycarbonyl-R q -oxyiminoacetamido)ceph-3-em-4-carboxylic acid (syn-isomer) which was characterised by optical rotation and/or by spectroscopy.

Workup

  1. customThe mixture was then evaporated to dryness
  2. dissolutiondissolved in acetone
  3. customwas removed under reduced pressure
  4. extractionthe product extracted into ethyl acetate (alternatively ether or methylene chloride
  5. washThe organic layer was washed with water and/or saturated brine
  6. customdried
  7. customevaporated

Sources & evidence

ORD record
ord-1b62e1a1190e42c2b90f38c7fbf636ad
Source dataset
uspto-grants-1978_06
Patent number
US04095021

Linked notes

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