Phosphorus oxychloride → Benzhydryl 7-[2-benzhydryloxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-vinyl-3-cephem-4-carboxylate

HRID 905481Notes

Reaction equation

HRID 905481 reaction equation
P(Cl)(Cl)(Cl)=O.[CH:6]([O:19][C:20]([CH2:22][O:23][N:24]=[C:25]([C:29]1[N:30]=[C:31]([NH:34][CH:35]=[O:36])[S:32][CH:33]=1)[C:26]([OH:28])=O)=[O:21])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Cl.[NH2:38][CH:39]1[C:64](=[O:65])[N:41]2[C:42]([C:48]([O:50][CH:51]([C:58]3[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=3)[C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)=[O:49])=[C:43]([CH:46]=[CH2:47])[CH2:44][S:45][C@H:40]12.C[Si](CC(N)=O)(C)C>O1CCCC1.C(OCC)(=O)C.O.CN(C)C=O>[CH:6]([O:19][C:20]([CH2:22][O:23][N:24]=[C:25]([C:29]1[N:30]=[C:31]([NH:34][CH:35]=[O:36])[S:32][CH:33]=1)[C:26]([NH:38][CH:39]1[C:64](=[O:65])[N:41]2[C:42]([C:48]([O:50][CH:51]([C:52]3[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=3)[C:58]3[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=3)=[O:49])=[C:43]([CH:46]=[CH2:47])[CH2:44][S:45][C@H:40]12)=[O:28])=[O:21])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 12818005Benzhydryl 7-amino-3vinyl-3cephem-4-carboxylate hydrochlorideHCID 536480482-(2-Formamidothiazol-4-yl)-2-benzhydryloxycarbonylmethoxyiminoacetic acid

Product 1

HCID 131713340Benzhydryl 7-[2-benzhydryloxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-vinyl-3-cephem-4-carboxylateYield 93.9%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Vilsmeir reagent was prepared from phosphorus oxychloride (1.28 ml) and N,N-dimethylformamide (1.06 ml) in tetrahydrofuran (35 ml) in a usual manner. To the resultant suspension was added 2-benzhydryloxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (5 g) under ice-cooling, and the mixture was stirred at the same temperature for 30 minutes to prepare the activated acid solution. This solution was added at a time to a solution of benzhydryl 7-amino-3-vinyl-3-cephem-4-carboxylate hydrochloride (4.89 g) and trimethylsilylacetamide (9.2 g) in ethyl acetate (40 ml) at -20° C., followed by stirring at -20° to -10° C. for an hour. After water and ethyl acetate were added to the reaction mixture, the separated organic layer was washed with 5% aqueous sodium carbonate and an aqueous sodium chloride, followed by drying over magnesium sulfate. Removal of the solvent gave benzhydryl 7-[2-benzhydryloxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-vinyl-3-cephem-4-carboxylate (syn isomer) (8.7 g).

Workup

  1. temperaturecooling
  2. customto prepare the activated acid solution
  3. stirringby stirring at -20° to -10° C. for an hour
  4. washthe separated organic layer was washed with 5% aqueous sodium carbonate
  5. dry with materialby drying over magnesium sulfate
  6. customRemoval of the solvent

Sources & evidence

ORD record
ord-38933c2fc3204732ac944ae6d4394790
Source dataset
uspto-grants-1983_12
Patent number
US04423213

Reaction notes

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