Phosphorus oxychloride → Benzhydryl 7-[2-(2-aminothiazol-4-yl)-2-(2,2,2-trichloroethoxycarbonylmethoxyimino)acetamido]-3-vinyl-3-cephem-4-carboxylate

HRID 1656248Notes

Reaction equation

HRID 1656248 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:11][O:12][CH2:13][C:14]([O:16][CH2:17][C:18]([Cl:21])([Cl:20])[Cl:19])=[O:15])[C:8]([OH:10])=O)[N:6]=1.P(Cl)(Cl)(Cl)=O.C[Si](CC(N)=O)(C)C.Cl.[NH2:36][CH:37]1[C:62](=[O:63])[N:39]2[C:40]([C:46]([O:48][CH:49]([C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)[C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)=[O:47])=[C:41]([CH:44]=[CH2:45])[CH2:42][S:43][C@H:38]12>C(OCC)(=O)C.O.CN(C)C=O>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:11][O:12][CH2:13][C:14]([O:16][CH2:17][C:18]([Cl:21])([Cl:20])[Cl:19])=[O:15])[C:8]([NH:36][CH:37]2[C:62](=[O:63])[N:39]3[C:40]([C:46]([O:48][CH:49]([C:50]4[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=4)[C:56]4[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=4)=[O:47])=[C:41]([CH:44]=[CH2:45])[CH2:42][S:43][C@H:38]23)=[O:10])[N:6]=1

Participants

8

Reactant 4

HCID 24813Phosphorus oxychloride2×HCID 357676Acetamide, 2-(trimethylsilyl)-2×HCID 12818005Benzhydryl 7-amino-3vinyl-3cephem-4-carboxylate hydrochlorideHCID 867391642-(2-Aminothiazol-4-yl)-2-(2,2,2-trichloroethoxycarbonylmethoxyimino)acetic acid

Product 1

HCID 131713346Benzhydryl 7-[2-(2-aminothiazol-4-yl)-2-(2,2,2-trichloroethoxycarbonylmethoxyimino)acetamido]-3-vinyl-3-cephem-4-carboxylateYield 83.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

To a mixture of 2-(2-aminothiazol-4-yl)-2-(2,2,2-trichloroethoxycarbonylmethoxyimino)acetic acid (syn isomer) (1.13 g) and phosphorus oxychloride (0.56 g) in ethyl acetate (20 ml) was added trimethylsilylacetamide (0.30 g) at 4° C., and the mixture was stirred at 4° to 6° C. for 15 minutes. To the mixture was added additional phosphorus oxychloride (0.56 g), followed by stirring at the same temperature for 15 minutes. Thereto was added N,N-dimethylformamide (0.26 g), and the mixture was stirred at 4° to 6° C. for 50 minutes to prepare the activated acid solution. This solution was added to a solution of benzhydryl 7-amino-3-vinyl-3-cephem-4-carboxylate hydrochloride (1.1 g) and trimethylsilylacetamide (2.0 g) in ethyl acetate (20 ml) at -20° C., and the mixture was stirred at -20° to 0° C. for an hour. After addition of ethyl acetate and water, the organic layer was separated and washed with a saturated aqueous sodium bicarbonate and an aqueous sodium chloride, followed by drying over magnesium sulfate. The solution was evaporated, and the residue was pulverized with diethyl ether to give benzhydryl 7-[2-(2-aminothiazol-4-yl)-2-(2,2,2-trichloroethoxycarbonylmethoxyimino)acetamido]-3-vinyl-3-cephem-4-carboxylate (syn isomer) (1.6 g).

Workup

  1. stirringby stirring at the same temperature for 15 minutes
  2. stirringthe mixture was stirred at 4° to 6° C. for 50 minutes
  3. customto prepare the activated acid solution
  4. stirringthe mixture was stirred at -20° to 0° C. for an hour
  5. customthe organic layer was separated
  6. washwashed with a saturated aqueous sodium bicarbonate
  7. dry with materialby drying over magnesium sulfate
  8. customThe solution was evaporated

Sources & evidence

ORD record
ord-98a90b82598840f897008040c609be76
Source dataset
uspto-grants-1993_10
Patent number
US05252731

Reaction notes

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