反応 #451716

反応方程式

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

4-nitrobenzyl 7-amino-3-hydroxy-3-cephem-4-carboxylate

trimethylsilylacetamide

bis(trimethylsilyl)acetamide

Phosphoryl chloride

→

4-nitrobenzyl 7-[2-(2-formamido-4-thiazolyl)-2-methoxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylate

収率 43.7%

溶媒

ethyl acetate

ethyl acetate

N,N-dimethylformamide

Ethyl acetate

Water

反応条件

後処理

1. 1
   workup.STIRRINGthe solution was stirred at 0° to 5° C. for 40 minutes
2. 2
   workup.STIRRINGstirred at -20° to -15° C. for 1.2 hours
3. 3
   workup.STIRRINGstirred until the temperature
4. 4
   その他rise 5° C
5. 5
   その他The aqueous layer was separated
6. 6
   抽出extracted with ethyl acetate
7. 7
   抽出The ethyl acetate layer and extract
8. 8
   洗浄washed with a saturated aqueous solution of sodium chloride
9. 9
   乾燥dried over magnesium sulfate
10. 10
    濃縮After the solution was concentrated to a volume of 50 ml
11. 11
    ろ過under reduced pressure, the precipitates were collected by filtration
12. 12
    洗浄washed with ethyl acetate

実験手順

Phosphoryl chloride (2.87 g.) was dropwise added to a solution of N,N-dimethylformamide (1.37 g.) in ethyl acetate (10 ml.) at 5° to 10° C. Ethyl acetate (40 ml.) was added to the solution, and stirred under ice cooling for 40 minutes. To the solution was added 2-(2-formamido-4-thiazolyl)-2-methoxyiminoacetic acid (syn isomer, 3.58 g.), and the solution was stirred at 0° to 5° C. for 40 minutes. The resultant solution was added all at once to a mixture of 4-nitrobenzyl 7-amino-3-hydroxy-3-cephem-4-carboxylate (5 g.), ethyl acetate (50 ml.), trimethylsilylacetamide (14.3 g.) and bis(trimethylsilyl)acetamide (5.8 g.) at -15° C., and stirred at -20° to -15° C. for 1.2 hours. Water (50 ml.) was added to the resultant solution at -25° to -20° C., and stirred until the temperature rise 5° C. The aqueous layer was separated and extracted with ethyl acetate. The ethyl acetate layer and extract were combined, washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After the solution was concentrated to a volume of 50 ml. under reduced pressure, the precipitates were collected by filtration and washed with ethyl acetate to give 4-nitrobenzyl 7-[2-(2-formamido-4-thiazolyl)-2-methoxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylate (syn isomer, 3.5 g.), mp 163° C. (dec.).

出典