Phosphorus oxychloride → 2-Methyl-7-[2-hexyloxyimino-2-(2-formylaminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

HRID 1155176Notes

Reaction equation

HRID 1155176 reaction equation
P(Cl)(Cl)(Cl)=O.[CH2:6]([O:12][N:13]=[C:14]([C:18]1[N:19]=[C:20]([NH:23][CH:24]=[O:25])[S:21][CH:22]=1)[C:15]([OH:17])=O)[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[CH3:26][CH:27]1[CH:32]=[C:31]([C:33]([OH:35])=[O:34])[N:30]2[C:36](=[O:39])[CH:37]([NH2:38])[C@H:29]2[S:28]1.C[Si](CC(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[CH3:26][CH:27]1[CH:32]=[C:31]([C:33]([OH:35])=[O:34])[N:30]2[C:36](=[O:39])[CH:37]([NH:38][C:15](=[O:17])[C:14](=[N:13][O:12][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[C:18]3[N:19]=[C:20]([NH:23][CH:24]=[O:25])[S:21][CH:22]=3)[C@H:29]2[S:28]1

Participants

9

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 128022512-Methyl-7-amino-3-cephem-4-carboxylic acidHCID 545208242-Hexyloxyimino-2-(2-formylaminothiazol-4-yl)acetic acidHCID 178445238HCID 178445238, compound

Product 1

HCID 1317125502-Methyl-7-[2-hexyloxyimino-2-(2-formylaminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
-20 °C

Procedure

To a solution of N,N-dimethylformamide (1.23 g) and ethyl acetate (9 ml) was added dropwise phosphorus oxychloride (2.58 g) at -10° to -5° C. with stirring, and the mixture was stirred for 30 minute at the same temperature. To the mixture were added 2-hexyloxyimino-2-(2-formylaminothiazol-4-yl)acetic acid (syn isomer), which can be represented as 2-hexyloxyimino-2-(2-formylimino-2,3-dihydrothiazol-4-yl)acetic acid (syn isomer), (4.2 g) and ethyl acetate (33 ml), and the mixture was stirred for 30 minutes at -10° to -5° C. and then cooled to -20° C. Thus obtained solution was added to a solution, which was prepared by stirring a mixture of 2-methyl-7-amino-3-cephem-4-carboxylic acid (3 g) and trimethylsilylacetamide (11 g) in ethyl acetate (33 ml), with stirring under cooling to -10° C. The mixture was stirred for 30 minutes at -10° C. and thereto was added water 50 ml. The mixture was extracted twice with ethyl acetate. The combined extracts were washed with an aqueous solution of sodium chloride and the precipitates were collected by filtration and then dried to give 2-methyl-7-[2-hexyloxyimino-2-(2-formylaminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid (syn isomer), which can be represented as 2-methyl-7-[2-hexyloxyimino-2-(2-formylimino-2,3-dihydrothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid (syn isomer), (4.3 g). The filtrate was evaporated to give further the same object compound (1.15 g).

Workup

  1. stirringthe mixture was stirred for 30 minute at the same temperature
  2. stirringthe mixture was stirred for 30 minutes at -10° to -5° C.
  3. additionThus obtained solution was added to a solution, which
  4. customwas prepared
  5. stirringby stirring
  6. stirringwith stirring
  7. temperatureunder cooling to -10° C
  8. stirringThe mixture was stirred for 30 minutes at -10° C.
  9. extractionThe mixture was extracted twice with ethyl acetate
  10. washThe combined extracts were washed with an aqueous solution of sodium chloride
  11. filtrationthe precipitates were collected by filtration
  12. customdried

Sources & evidence

ORD record
ord-909091a5e18349fb8a242c300e3147e8
Source dataset
uspto-grants-1981_11
Patent number
US04299829

Reaction notes

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