Reaction #155338

Reaction equation

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

Yield 50.0%

Solvents

ethanol

Conditions

Workup

1. 1
   ConcentrationThe resulting mixture was concentrated under reduced pressure
2. 2
   workup.ADDITIONWater was added to the residue, which
3. 3
   Washwas then washed with ethyl acetate
4. 4
   workup.ADDITIONA 2N aqueous sodium hydroxide solution (6 ml) was added to the water layer
5. 5
   Extractionfollowed by extraction with dichloromethane
6. 6
   WashThe thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution
7. 7
   Dryingdried over anhydrous magnesium sulfate
8. 8
   Concentrationconcentrated under reduced pressure
9. 9
   OtherThe residue was purified
10. 10
    ConcentrationThe 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
    Concentrationconcentrated to dryness under reduced pressure
15. 15
    Otherrecrystallized from ethyl acetate

Procedure

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%).

Source