Phosphorus oxychloride → Sodium 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-3-hydroxycepham-4-carboxylate

HRID 2296220Notes

Reaction equation

HRID 2296220 reaction equation
P(Cl)(Cl)(Cl)=O.[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH3:20])[C:15]([OH:17])=O)[N:13]=1)=[O:7].[NH2:21][CH:22]1[C:33](=[O:34])[N:24]2[CH:25]([C:30]([OH:32])=[O:31])[CH:26]([OH:29])[CH2:27][S:28][C@H:23]12.C[Si](CC(N)=O)(C)C.C(=O)(O)[O-].[Na+:47]>C(OCC)(=O)C.O.CN(C)C=O>[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH3:20])[C:15]([NH:21][CH:22]2[C:33](=[O:34])[N:24]3[CH:25]([C:30]([O-:32])=[O:31])[CH:26]([OH:29])[CH2:27][S:28][C@H:23]23)=[O:17])[N:13]=1)=[O:7].[Na+:47]

Participants

9

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 27245112-(2-Formylamino-1,3-Thiazol-4-Yl)-2-(Methoxyimino)Acetic AcidHCID 13072520(6R)-7-amino-3-hydroxy-8-oxo-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylic acid

Product 1

HCID 86738039Sodium 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-3-hydroxycepham-4-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Phosphoryl chloride (704 mg.) was added dropwise to a solution of N,N-dimethylformamide (336 mg.) in ethyl acetate (8 ml.) below 5° C. and stirred at the same temperature for 30 minutes. 2-(2-Formamidothiazol-4-yl)-2-methoxyiminoacetic acid (syn isomer, 1 g.) was added to the solution and stirred at 5° to 10° C. for an hour. The solution was added dropwise to a solution of 7-amino-3-hydroxycepham-4-carboxylic acid (872 mg.) and trimethylsilylacetamide (1.05 g.) in ethyl acetate (20 ml.) at -20° C. over 5 minutes, and stirred at -20° to -25° C. for an hour. Water (50 ml.) was added to the resultant solution and adjusted to pH 7.0 with sodium bicarbonate. The aqueous layer was separated, and the ethyl acetate layer was extracted again with water (10 ml.). The aqueous extracts were combined, adjusted to pH 6 and absorbed on macroporous nonionic absorption resin Diaion HP-20 (50 ml., Trademark, manufactured by Mitsubishi Chemical Industries). The column was washed with water (50 ml.) and eluted with 30% aqueous isopropyl alcohol. The eluate containing the object compound was adjusted to pH 6.5 and concentrated under reduced pressure. The residue was lyophilized to give sodium 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-3-hydroxycepham-4-carboxylate (syn isomer, 1.1 g.)

Workup

  1. stirringstirred at 5° to 10° C. for an hour
  2. stirringstirred at -20° to -25° C. for an hour
  3. customThe aqueous layer was separated
  4. extractionthe ethyl acetate layer was extracted again with water (10 ml.)
  5. customabsorbed on macroporous nonionic absorption resin Diaion HP-20 (50 ml., Trademark, manufactured by Mitsubishi Chemical Industries)
  6. washThe column was washed with water (50 ml.)
  7. washeluted with 30% aqueous isopropyl alcohol
  8. additionThe eluate containing the object compound
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d9a16dddf05b49b7b10a3edb6d008491
Source dataset
uspto-grants-1984_01
Patent number
US04427674

Reaction notes

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