Phosphorus oxychloride → Benzhydryl 7-[2-methoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(2,2-dichlorovinyl)-3-cephem-4-carboxylate

HRID 64751

Reaction equation

HRID 64751 reaction equation
C[N+](C)=CCl.[Cl-].P(Cl)(Cl)(Cl)=O.[CH3:12][O:13][N:14]=[C:15]([C:19]1[N:20]=[C:21]([NH:24][CH:25]=[O:26])[S:22][CH:23]=1)[C:16]([OH:18])=O.Cl.[NH2:28][CH:29]1[C:56](=[O:57])[N:31]2[C:32]([C:40]([O:42][CH:43]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[O:41])=[C:33]([CH:36]=[C:37]([Cl:39])[Cl:38])[CH2:34][S:35][C@H:30]12>O1CCCC1.C(OCC)(=O)C.O.CN(C)C=O>[CH3:12][O:13][N:14]=[C:15]([C:19]1[N:20]=[C:21]([NH:24][CH:25]=[O:26])[S:22][CH:23]=1)[C:16]([NH:28][CH:29]1[C:56](=[O:57])[N:31]2[C:32]([C:40]([O:42][CH:43]([C:50]3[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=3)[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[O:41])=[C:33]([CH:36]=[C:37]([Cl:39])[Cl:38])[CH2:34][S:35][C@H:30]12)=[O:18]

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 27245112-(2-Formylamino-1,3-Thiazol-4-Yl)-2-(Methoxyimino)Acetic AcidHCID 88625735Benzhydryl 7-amino-3-(2,2-dichlorovinyl)-3-cephem-4-carboxylate hydrochloride

Product 1

HCID 131714844Benzhydryl 7-[2-methoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(2,2-dichlorovinyl)-3-cephem-4-carboxylateYield 67.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a stirred suspension of Vilsmeier reagent prepared from N,N-dimethylformamide (0.56 ml) and phosphorus oxychloride (0.664 ml) in tetrahydrofuran (11 ml) in a usual manner was added 2-methoxyimino-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (1.38 g) under ice-cooling and the mixture was stirred for 30 minutes at the same temperature. To a solution of benzhydryl 7-amino-3-(2,2-dichlorovinyl)-3-cephem-4-carboxylate hydrochloride (2.5 g) and monotrimethylsilylacetamide (3.95 g) in ethyl acetate (25 ml) was added the activated acid solution obtained above at -20° C. and mixture was stirred at -20° to -10° C. for 30 minutes. After water and ethyl acetate were added to the resultant mixture, the separated organic layer was washed in turn with saturated aqueous sodium bicarbonate and brine, dried over magnesium sulfate. The solution was evaporated in vacuo to give benzhydryl 7-[2-methoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(2,2-dichlorovinyl)-3-cephem-4-carboxylate (syn isomer) (2.28 g).

Workup

  1. temperaturecooling
  2. customobtained above at -20° C. and mixture
  3. stirringwas stirred at -20° to -10° C. for 30 minutes
  4. washthe separated organic layer was washed in turn with saturated aqueous sodium bicarbonate and brine
  5. dry with materialdried over magnesium sulfate
  6. customThe solution was evaporated in vacuo

Sources & evidence

ORD record
ord-0cc3ce44be43458c812d219a359ea1f3
Source dataset
uspto-grants-1986_09
Patent number
US04609730

Linked notes

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