Sodium Hydroxide → 4-[3-(3-Fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(3,4,5-trifluorophenoxy)ethyl]piperidine-4-carboxylic acid

HRID 1071270Notes

Reaction equation

HRID 1071270 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][CH2:14][C:15]1([C:33]([O:35]CC)=[O:34])[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][O:23][C:24]3[CH:29]=[C:28]([F:30])[C:27]([F:31])=[C:26]([F:32])[CH:25]=3)[CH2:17][CH2:16]1)=[CH:9][C:8]([O:38][CH3:39])=[CH:7][CH:6]=2.[OH-].[Na+]>O1CCOCC1.CO>[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][CH2:14][C:15]1([C:33]([OH:35])=[O:34])[CH2:16][CH2:17][N:18]([CH2:21][CH2:22][O:23][C:24]3[CH:29]=[C:28]([F:30])[C:27]([F:31])=[C:26]([F:32])[CH:25]=3)[CH2:19][CH2:20]1)=[CH:9][C:8]([O:38][CH3:39])=[CH:7][CH:6]=2

Participants

5

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 22469890Ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(3,4,5-trifluorophenoxy)ethyl]piperidine-4-carboxylate

Product 1

HCID 224685714-[3-(3-Fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(3,4,5-trifluorophenoxy)ethyl]piperidine-4-carboxylic acidYield 77.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 0.8 g of ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(3,4,5-trifluoro-phenoxy)ethyl]piperidine-4-carboxylate in 50 cm3 of dioxane, 50 cm3 of methanol and 4.4 cm3 of aqueous 5N sodium hydroxide solution was stirred at a temperature in the region of 70° C. for 18 hours. A further 4.4 cm3 of aqueous 5N sodium hydroxide solution were added to the reaction mixture, which was stirred for 6 hours in the region of 70° C. After cooling to about 20° C., the reaction mass was concentrated to dryness under reduced pressure (1.1 kPa) at a temperature in the region of 50° C. The residue was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 4 cm; height 20 cm), eluting with a mixture of chloroform/methanol/aqueous ammonia (12/3/0.5 by volume) and collecting 60-cm3 fractions. Fractions 8 to 19 were combined, concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. and oven-dried under reduced pressure (10 kPa) at about 50° C. 0.59 g of 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(3,4,5-trifluorophenoxy)ethyl]piperidine-4-carboxylic acid was obtained in the form of a white solid melting at about 120° C.

Workup

  1. stirringwas stirred for 6 hours in the region of 70° C
  2. temperatureAfter cooling to about 20° C.
  3. concentrationthe reaction mass was concentrated to dryness under reduced pressure (1.1 kPa) at a temperature in the region of 50° C
  4. customThe residue was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 4 cm; height 20 cm)
  5. washeluting with a mixture of chloroform/methanol/aqueous ammonia (12/3/0.5 by volume)
  6. customcollecting 60-cm3 fractions
  7. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C.
  8. customoven-dried under reduced pressure (10 kPa) at about 50° C

Sources & evidence

ORD record
ord-9a78851bc8144e08b2243560b2850a9e
Source dataset
uspto-grants-2005_06
Patent number
US06903217B2

Reaction notes

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