Phosphorus oxychloride → Benzhydryl 7-(4-chloro-2-methoxycarbonylmethoxyimino-3-oxobutyramido)-3-vinyl-3-cephem-4-carboxylate

HRID 569447Notes

Reaction equation

HRID 569447 reaction equation
P(Cl)(Cl)(Cl)=O.[Cl:6][CH2:7][C:8](=[O:20])[C:9](=[N:13][O:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])[C:10]([OH:12])=O.Cl.[NH2:22][CH:23]1[C:48](=[O:49])[N:25]2[C:26]([C:32]([O:34][CH:35]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[O:33])=[C:27]([CH:30]=[CH2:31])[CH2:28][S:29][C@H:24]12.C[Si](CC(N)=O)(C)C>O1CCCC1.C(OCC)(=O)C.O.CN(C)C=O>[Cl:6][CH2:7][C:8](=[O:20])[C:9](=[N:13][O:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])[C:10]([NH:22][CH:23]1[C:48](=[O:49])[N:25]2[C:26]([C:32]([O:34][CH:35]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)[C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[O:33])=[C:27]([CH:30]=[CH2:31])[CH2:28][S:29][C@H:24]12)=[O:12]

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 12818005Benzhydryl 7-amino-3vinyl-3cephem-4-carboxylate hydrochlorideHCID 248204364-Chloro-2-methoxycarbonylmethoxyimino-3-oxobutyric acid

Product 1

HCID 131714061Benzhydryl 7-(4-chloro-2-methoxycarbonylmethoxyimino-3-oxobutyramido)-3-vinyl-3-cephem-4-carboxylateYield 93.7%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Vilsmeir reagent prepared from N,N-dimethylformamide (3.4 g) and phosphorus oxychloride (7.1 g) was suspended in dry tetrahydrofuran (30 ml). To the suspension was added 4-chloro-2-methoxycarbonylmethoxyimino-3-oxobutyric acid (syn isomer) (10 g) under ice-cooling, and the mixture was stirred at the same temperature for an hour 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 (16.3 g) and trimethylsilylacetamide (40 g) in ethyl acetate (163 ml) at -30° C. After the reaction mixture was stirred at -15° C. for an hour, the resultant solution was poured into water (100 ml) and then extracted with ethyl acetate (200 ml). The extract was washed with a saturated aqueous sodium bicarbonate and a saturated aqueous sodium chloride. The organic layer was dried over magnesium sulfate and evaporated under reduced pressure to give benzhydryl 7-(4-chloro-2-methoxycarbonylmethoxyimino-3-oxobutyramido)-3-vinyl-3-cephem-4-carboxylate (syn isomer) (21.8 g).

Workup

  1. temperaturecooling
  2. customto prepare the activated acid solution
  3. stirringAfter the reaction mixture was stirred at -15° C. for an hour
  4. extractionextracted with ethyl acetate (200 ml)
  5. washThe extract was washed with a saturated aqueous sodium bicarbonate
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-dec50f061ecf4aefae6d1c6ff5636124
Source dataset
uspto-grants-1988_03
Patent number
US04731443

Reaction notes

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