反応 #155338

反応方程式

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

収率 50.0%

溶媒

ethanol

反応条件

後処理

1. 1
   濃縮The resulting mixture was concentrated under reduced pressure
2. 2
   workup.ADDITIONWater was added to the residue, which
3. 3
   洗浄was then washed with ethyl acetate
4. 4
   workup.ADDITIONA 2N aqueous sodium hydroxide solution (6 ml) was added to the water layer
5. 5
   抽出followed by extraction with dichloromethane
6. 6
   洗浄The thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution
7. 7
   乾燥dried over anhydrous magnesium sulfate
8. 8
   濃縮concentrated under reduced pressure
9. 9
   その他The residue was purified
10. 10
    濃縮The 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
    濃縮concentrated to dryness under reduced pressure
15. 15
    その他recrystallized from ethyl acetate

実験手順

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%).

出典