반응 #155338

반응 방정식

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

수율 50.0%

용매

ethanol

반응 조건

후처리

1. 1
   농축The resulting mixture was concentrated under reduced pressure
2. 2
   workup.ADDITIONWater was added to the residue, which
3. 3
   세척was then washed with ethyl acetate
4. 4
   workup.ADDITIONA 2N aqueous sodium hydroxide solution (6 ml) was added to the water layer
5. 5
   추출followed by extraction with dichloromethane
6. 6
   세척The thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution
7. 7
   건조dried over anhydrous magnesium sulfate
8. 8
   농축concentrated under reduced pressure
9. 9
   기타The residue was purified
10. 10
    농축The 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
    농축concentrated to dryness under reduced pressure
15. 15
    기타recrystallized from ethyl acetate

실험 절차

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%).

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