Hydrogen chloride-ethyl acetate → 2-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]-N-piperidin-4-ylacetamide

HRID 1474538Notes

Reaction equation

HRID 1474538 reaction equation
C(OC(=O)C)C.Cl.[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:48])[C:12]([C:40]1[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=1)=[CH:13][N:14]2[CH2:23][C:24]([NH:26][CH:27]1[CH2:32][CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29][CH2:28]1)=[O:25]>C(O)C>[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:48])[C:12]([C:40]1[CH:41]=[CH:42][C:43]([O:46][CH3:47])=[CH:44][CH:45]=1)=[CH:13][N:14]2[CH2:23][C:24]([NH:26][CH:27]1[CH2:28][CH2:29][NH:30][CH2:31][CH2:32]1)=[O:25]

Participants

4

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 56598734HCID 56598734, compound

Product 1

HCID 674632432-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]-N-piperidin-4-ylacetamideYield 27.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A 4N hydrochloric acid ethyl acetate solution (25 ml) was added to an ethanol solution (12 ml) of tert-butyl 4-{2-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]acetylamino}piperidine-1-carboxylate (820 mg, 1.44 mmol), followed by stirring at room temperature for 28 hours. The resulting mixture was concentrated under reduced pressure. After adding an aqueous sodium bicarbonate solution to the residue to adjust the pH to 8, the residue was washed with ethyl acetate. A 2N aqueous sodium hydroxide solution was added to the water layer to adjust its pH to 11, followed by extraction using dichloromethane. The thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution and dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was recrystallized from ethanol-ethyl acetate, giving a white powder of 2-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]-N-piperidin-4-ylacetamide (185 mg, yield: 27%).

Workup

  1. concentrationThe resulting mixture was concentrated under reduced pressure
  2. additionAfter adding an aqueous sodium bicarbonate solution to the residue
  3. washthe residue was washed with ethyl acetate
  4. additionA 2N aqueous sodium hydroxide solution was added to the water layer
  5. extractionfollowed by extraction
  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 recrystallized from ethanol-ethyl acetate

Sources & evidence

ORD record
ord-fdd2df7ad7ac45b5ba7afebdf5cbb10d
Source dataset
uspto-grants-2015_04
Patent number
US09018229B2

Reaction notes

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