Reaction #93029

Reaction equation

2-methoxyimino-2-(2-formamidothiazol-4-yl)acetic acid

Vilsmeier reagent

benzhydryl 7-amino-3-(2,2-dichlorovinyl)-3-cephem-4-carboxylate hydrochloride

phosphorus oxychloride

→

benzhydryl 7-[2-methoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(2,2-dichlorovinyl)-3-cephem-4-carboxylate

Yield 67.5%

Solvents

ethyl acetate

water

ethyl acetate

tetrahydrofuran

N,N-dimethylformamide

Conditions

Workup

1. 1
   Temperaturecooling
2. 2
   Otherobtained above at -20° C. and mixture
3. 3
   workup.STIRRINGwas stirred at -20° to -10° C. for 30 minutes
4. 4
   Washthe separated organic layer was washed in turn with saturated aqueous sodium bicarbonate and brine
5. 5
   Dryingdried over magnesium sulfate
6. 6
   OtherThe solution was evaporated in vacuo

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).

Source