反应详情

In 10 ml of methylene chloride was dissolved 0.96 g of 2-[4-[3-(benzyloxy)-3-oxopropyl]-8-(3-methylbutylidene)-3-oxo-1-thia-4-azaspiro[4.5]decan-2-yl]-acetic acid. After adding 0.18 ml of thionyl chloride at ambient temperature, the resulting mixture was stirred for one hour under reflux. The reaction mixture was concentrated under reduced pressure, and the concentrate was dissolved in 10 ml of dioxane. The resulting solution was dropwise added at 0-5° C. to an ethyl ether solution containing diazomethane prepared from 5.00 g of N-methylnitrosourea, 3.00 g of potassium hydroxide, 4.00 ml of water and 15 ml of ethyl ether, and the resulting mixture was stirred at ambient temperature for 30 minutes. The reaction mixture was poured into a mixture of water, acetic acid and ethyl acetate, and the organic layer was separated. The organic layer thus obtained was washed successively with water, saturated aqueous solution of sodium hydrogen carbonate and saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was dissolved in a mixture of 10 ml dioxane and 10 ml water, and the resulting solution was added to a mixture of 0.16 g of silver benzoate and 3.00 ml of triethylamine at ambient temperature and stirred for 2 hours. The reaction mixture was poured into a mixture of water and ethyl acetate, pH was adjusted to 2.0 with 2 mol/L hydrochloric acid, and the organic layer was separated. The organic layer thus obtained was washed successively with water and saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Purification of the residue by column chromatography [eluent: chloroform:ethanol=80:1] gave 0.36 g of 3-[4-[3-(benzyloxy)-3-oxopropyl]-8-(3-methylbutylidene)-3-oxo-1-thia-4-azaspiro[4.5]decan-2-yl]-propionic acid as a light yellow oily product.

1. temperatureunder reflux
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. dissolutionthe concentrate was dissolved in 10 ml of dioxane
4. additionThe resulting solution was dropwise added at 0-5° C. to an ethyl ether solution
5. additioncontaining diazomethane
6. customprepared from 5.00 g of N-methylnitrosourea, 3.00 g of potassium hydroxide, 4.00 ml of water and 15 ml of ethyl ether
7. stirringthe resulting mixture was stirred at ambient temperature for 30 minutes
8. customthe organic layer was separated
9. customThe organic layer thus obtained
10. washwas washed successively with water, saturated aqueous solution of sodium hydrogen carbonate and saturated aqueous solution of sodium chloride
11. dry with materialdried over anhydrous magnesium sulfate
12. distillationthe solvent was distilled off under reduced pressure
13. dissolutionThe residue was dissolved in a mixture of 10 ml dioxane and 10 ml water
14. additionthe resulting solution was added to a mixture of 0.16 g of silver benzoate and 3.00 ml of triethylamine at ambient temperature
15. stirringstirred for 2 hours
16. additionThe reaction mixture was poured into a mixture of water and ethyl acetate, pH
17. customthe organic layer was separated
18. customThe organic layer thus obtained
19. washwas washed successively with water and saturated aqueous solution of sodium chloride
20. dry with materialdried over anhydrous magnesium sulfate
21. distillationthe solvent was distilled off under reduced pressure
22. customPurification of the residue by column chromatography [eluent: chloroform:ethanol=80:1]