反应详情

In 30 ml. of anhydrous pyridine there were dissolved 4g. of 3-amino-4-benzyloxy-α-[N-benzyl-N-(1-methyl-2-p-hydroxyphenylethyl)-aminomethyl]benzyl alcohol hydrochloride and 3.5 g of N-acetyl-β-alanine and after adding to the solution 5.5 g. of dicyclohexylcarbodiimide under ice-cooling, the mixture was stirred overnight. After filtering off the precipitates thus formed, the reaction mixture was concentrated under reduced pressure and the residue was dissolved in 30 ml. of methanol. Then, after adding to the solution 10 ml. of 4N sodium hydroxide solution, the mixture was stirred for 3 hours and further after adding thereto 1N hydrochloric acid solution to adjust the pH to 3 and adding excessive sodium carbonate, the resultant mixture was stirred for 30 minutes. The reaction product was concentrated under a reduced pressure and then extracted with 50 ml. of chloroform. The extract was washed three times with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to five 4 g. of a yellow oily material. By subjecting the product to a silica gel column chromatography (75 ml.) and further to a silica gel column chromatography (35 ml.), 800 mg. of a pure caramel-like 3-(N-acetyl-β-alanyl)amino-4-benzyloxy-α-[N-benzyl-N-(1-methyl-2-p-hydroxyphenylethyl)aminomethyl]benzyl alcohol was obtained. In the above chromatographic purification treatments, 4 : 2 : 1 ethyl acetate-benzene-methanol was used as the developing solvent.

1. filtrationAfter filtering off the
2. customprecipitates thus
3. customformed
4. concentrationthe reaction mixture was concentrated under reduced pressure
5. dissolutionthe residue was dissolved in 30 ml
6. additionThen, after adding to the solution 10 ml
7. stirringof 4N sodium hydroxide solution, the mixture was stirred for 3 hours
8. additionfurther after adding
9. additionadding excessive sodium carbonate
10. stirringthe resultant mixture was stirred for 30 minutes
11. concentrationThe reaction product was concentrated under a reduced pressure
12. extractionextracted with 50 ml
13. washThe extract was washed three times with water
14. dry with materialdried over anhydrous magnesium sulfate
15. concentrationconcentrated under reduced pressure to five 4 g