تفاعل #155338

معادلة التفاعل

hydrogen chloride ethyl acetate

tert-butyl((S)-1-{2-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]ethylcarbamoyl}-2-hydroxyethyl)carbamate

→

(S)-2-amino-N-{2-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]ethyl}-3-hydroxypropionamide hydrochloride

المردود 50.0%

المذيبات

ethanol

ظروف التفاعل

المعالجة

1. 1
   تركيزThe resulting mixture was concentrated under reduced pressure
2. 2
   workup.ADDITIONWater was added to the residue, which
3. 3
   غسيلwas then washed with ethyl acetate
4. 4
   workup.ADDITIONA 2N aqueous sodium hydroxide solution (6 ml) was added to the water layer
5. 5
   استخلاصfollowed by extraction with dichloromethane
6. 6
   غسيلThe thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution
7. 7
   تجفيفdried over anhydrous magnesium sulfate
8. 8
   تركيزconcentrated under reduced pressure
9. 9
   أخرىThe residue was purified
10. 10
    تركيزThe purified product was concentrated under reduced pressure
11. 11
    workup.DISSOLUTIONthe residue was dissolved in ethanol (3 ml)
12. 12
    workup.ADDITIONethyl acetate (3 ml), and a 4N hydrogen chloride ethylacetate solution (0.1 ml) was then added
13. 13
    workup.STIRRINGThe mixture was stirred
14. 14
    تركيزconcentrated to dryness under reduced pressure
15. 15
    أخرىrecrystallized from ethyl acetate

الإجراء التجريبي

A 4N hydrogen chloride ethyl acetate solution (5 ml) was added to an ethanol solution (5 ml) of tert-butyl((S)-1-{2-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]ethylcarbamoyl}-2-hydroxyethyl)carbamate (330 mg, 0.6 mmol) and stirred at room temperature for 14 hours. The resulting mixture was concentrated under reduced pressure. Water was added to the residue, which was then washed with ethyl acetate. A 2N aqueous sodium hydroxide solution (6 ml) was added to the water layer to adjust its pH to 11, followed by extraction with dichloromethane. The thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified using silica gel column chromatography (dichloromethane:methanol=20:1→15:1). The purified product was concentrated under reduced pressure, the residue was dissolved in ethanol (3 ml) and ethyl acetate (3 ml), and a 4N hydrogen chloride ethylacetate solution (0.1 ml) was then added thereto. The mixture was stirred and concentrated to dryness under reduced pressure, and recrystallized from ethyl acetate, giving a white powder of (S)-2-amino-N-{2-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]ethyl}-3-hydroxypropionamide hydrochloride (145 mg, yield: 50%).

المصدر