Phosphorus oxychloride → 7-(2-Methoxyimino-3-oxo-4,4-dibromobutyramido)-3-hydroxycepham-4-carboxylic acid

HRID 1164262Notes

Reaction equation

HRID 1164262 reaction equation
[CH3:1][O:2][N:3]=[C:4]([C:8](=[O:12])[CH:9]([Br:11])[Br:10])[C:5]([OH:7])=O.P(Cl)(Cl)(Cl)=O.[NH2:18][CH:19]1[C:30](=[O:31])[N:21]2[CH:22]([C:27]([OH:29])=[O:28])[CH:23]([OH:26])[CH2:24][S:25][C@H:20]12.C[Si](CC(N)=O)(C)C>C(Cl)Cl.O.CN(C)C=O>[CH3:1][O:2][N:3]=[C:4]([C:8](=[O:12])[CH:9]([Br:11])[Br:10])[C:5]([NH:18][CH:19]1[C:30](=[O:31])[N:21]2[CH:22]([C:27]([OH:29])=[O:28])[CH:23]([OH:26])[CH2:24][S:25][C@H:20]12)=[O:7]

Participants

8

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 13072520(6R)-7-amino-3-hydroxy-8-oxo-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylic acidHCID 542636792-Methoxyimino-3-oxo-4,4-dibromobutyric acid

Product 1

HCID 867387467-(2-Methoxyimino-3-oxo-4,4-dibromobutyramido)-3-hydroxycepham-4-carboxylic acidYield 92.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

A solution of 2-methoxyimino-3-oxo-4,4-dibromobutyric acid (syn isomer, 10 g) in methylene chloride (10 ml) was added to a solution of N,N-dimethylformamide (2.89 g) and phosphoryl chloride (6.07 g) in methylene chloride (30 ml) at -15° to 10° C., and stirred for an hour. The solution was added to a solution of 7-amino-3-hydroxycepham-4-carboxylic acid (4.8 g) and trimethylsilylacetamide (23.1 g) in methylene chloride (100 ml) at -15° to -10° C., and stirred for 2 hours. To the resultant solution was added water (40 ml) under ice-cooling and stirred for 10 minutes, and then the solvent was removed under reduced pressure therefrom. To the residue was added a saturated aqueous solution of sodium chloride (40 ml) and allowed to stand in a refrigerator overnight. The precipitates were collected by filtration, washed with a saturated aqueous solution of sodium chloride and water in turn, and dried under reduced pressure to give 7-(2-methoxyimino-3-oxo-4,4-dibromobutyramido)-3-hydroxycepham-4-carboxylic acid (syn isomer, 10.27 g).

Workup

  1. stirringstirred for 2 hours
  2. temperaturecooling
  3. stirringstirred for 10 minutes
  4. customthe solvent was removed under reduced pressure
  5. additionTo the residue was added a saturated aqueous solution of sodium chloride (40 ml)
  6. customto stand in a refrigerator overnight
  7. filtrationThe precipitates were collected by filtration
  8. washwashed with a saturated aqueous solution of sodium chloride and water in turn
  9. customdried under reduced pressure

Sources & evidence

ORD record
ord-06272a7dcfc6422ebae44023615a8ab1
Source dataset
uspto-grants-1983_01
Patent number
US04368325

Reaction notes

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