Reacción #155338

Ecuación de reacción

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

Rendimiento 50.0%

Disolventes

ethanol

Condiciones de reacción

Tratamiento posterior

1. 1
   ConcentraciónThe resulting mixture was concentrated under reduced pressure
2. 2
   workup.ADDITIONWater was added to the residue, which
3. 3
   Lavadowas then washed with ethyl acetate
4. 4
   workup.ADDITIONA 2N aqueous sodium hydroxide solution (6 ml) was added to the water layer
5. 5
   Extracciónfollowed by extraction with dichloromethane
6. 6
   LavadoThe thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution
7. 7
   Secadodried over anhydrous magnesium sulfate
8. 8
   Concentraciónconcentrated under reduced pressure
9. 9
   OtroThe residue was purified
10. 10
    ConcentraciónThe 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
    Concentraciónconcentrated to dryness under reduced pressure
15. 15
    Otrorecrystallized from ethyl acetate

Procedimiento

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%).

Fuente