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

HRID 1474545Notes

Reaction equation

HRID 1474545 reaction equation
C(OC(=O)C)C.[ClH:7].[F:8][C:9]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][CH3:22])=[C:15]2[C:10]=1[C:11](=[O:47])[C:12]([C:39]1[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=1)=[CH:13][N:14]2[CH2:23][CH2:24][NH:25][C:26]([C@@H:28]([NH:31]C(=O)OC(C)(C)C)[CH2:29][OH:30])=[O:27]>C(O)C>[ClH:7].[NH2:31][C@@H:28]([CH2:29][OH:30])[C:26]([NH:25][CH2:24][CH2:23][N:14]1[C:15]2[C:10](=[C:9]([F:8])[CH:18]=[CH:17][C:16]=2[O:19][CH2:20][CH2:21][CH3:22])[C:11](=[O:47])[C:12]([C:39]2[CH:40]=[CH:41][C:42]([O:45][CH3:46])=[CH:43][CH:44]=2)=[CH:13]1)=[O:27]

Participants

4

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 68207133tert-butyl ((S)-1-{2-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]ethylcarbamoyl}-2-hydroxyethyl)carbamate

Product 1

HCID 67463736(S)-2-amino-N-{2-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]ethyl}-3-hydroxypropionamide hydrochlorideYield 50%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

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%).

Workup

  1. concentrationThe resulting mixture was concentrated under reduced pressure
  2. additionWater was added to the residue, which
  3. washwas then washed with ethyl acetate
  4. additionA 2N aqueous sodium hydroxide solution (6 ml) was added to the water layer
  5. extractionfollowed by extraction with dichloromethane
  6. washThe thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified
  10. concentrationThe purified product was concentrated under reduced pressure
  11. dissolutionthe residue was dissolved in ethanol (3 ml)
  12. additionethyl acetate (3 ml), and a 4N hydrogen chloride ethylacetate solution (0.1 ml) was then added
  13. stirringThe mixture was stirred
  14. concentrationconcentrated to dryness under reduced pressure
  15. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-32f0645d2dff443686a48debc17e0c0e
Source dataset
uspto-grants-2015_04
Patent number
US09018229B2

Reaction notes

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