反応 #451706

反応方程式

Vilsmeier reagent

phosphorus oxychloride

p-nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate

trimethylsilylacetamide

2-(2-Formamido-4-thiazolyl)-2-methoxyiminoacetic acid

→

p-nitrobenzyl 7-{2-(2-formamido-4-thiazolyl)-2-methoxyiminoacetamido}-3-chloro-3-cephem-4-carboxylate

収率 80.8%

溶媒

water

dimethylformamide

ethyl acetate

ethyl acetate

反応条件

後処理

1. 1
   温度cooling
2. 2
   workup.STIRRINGthe mixture was stirred at the same temperature for 30 minutes
3. 3
   その他to prepare the activated acid solution
4. 4
   workup.STIRRINGwith stirring
5. 5
   workup.STIRRINGthe mixed solution was stirred at -10° to -20° C. for 1.5 hours
6. 6
   workup.STIRRINGthe solution was stirred at -20° C
7. 7
   その他After separating the ethyl acetate layer
8. 8
   抽出the aqueous layer was extracted with ethyl acetate (20 ml.)
9. 9
   洗浄washed with 10% hydrochloric acid (20 ml.) twice
10. 10
    乾燥water (20 ml.) once, a 5% aqueous solution of sodium bicarbonate (20 ml.) three times, and an aqueous solution of sodium chloride (20 ml.) once in turn, dried
11. 11
    濃縮concentrated under reduced pressure
12. 12
    洗浄The residue was washed with diethyl ether (50 ml.)

実験手順

Vilsmeier reagent prepared from dimethylformamide (0.22 g.) and phosphorus oxychloride (0.46 g.) was suspended in dry ethyl acetate (20 ml.). 2-(2-Formamido-4-thiazolyl)-2-methoxyiminoacetic acid (anti isomer, 0.62 g.) was added to the suspension under ice-cooling with stirring, and the mixture was stirred at the same temperature for 30 minutes to prepare the activated acid solution. The solution was added all at once to a solution of p-nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate (1 g.) and trimethylsilylacetamide (2.58 g.) in ethyl acetate (20 ml.) at -20° C. with stirring, and the mixed solution was stirred at -10° to -20° C. for 1.5 hours. To the resultant solution was added water (20 ml), and the solution was stirred at -20° C. After separating the ethyl acetate layer, the aqueous layer was extracted with ethyl acetate (20 ml.). The ethyl acetate layer and the extract were combined together, washed with 10% hydrochloric acid (20 ml.) twice, water (20 ml.) once, a 5% aqueous solution of sodium bicarbonate (20 ml.) three times, and an aqueous solution of sodium chloride (20 ml.) once in turn, dried, and then concentrated under reduced pressure. The residue was washed with diethyl ether (50 ml.) to give p-nitrobenzyl 7-{2-(2-formamido-4-thiazolyl)-2-methoxyiminoacetamido}-3-chloro-3-cephem-4-carboxylate (anti isomer, 1.27 g.), m.p. 135° to 145° C. (dec.).

出典