Sodium Hydroxide → HCID 22468489, compound

HRID 395008Notes

Reaction equation

HRID 395008 reaction equation
[Cl: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:30]([O:32]CC)=[O:31])[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)[CH2:17][CH2:16]1)=[CH:9][C:8]([O:35][CH3:36])=[CH:7][CH:6]=2.[OH-].[Na+]>O1CCOCC1.CO>[Cl: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:30]([OH:32])=[O:31])[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)[CH2:17][CH2:16]1)=[CH:9][C:8]([O:35][CH3:36])=[CH:7][CH:6]=2

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 22469137HCID 22469137, compound

Product 1

HCID 22468489HCID 22468489, compoundYield 101.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 0.12 g of ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-[2-(pyridin-2-yloxy)-ethyl]piperidine-4-carboxylate in 5 cm3 of dioxane, 5 cm3 of methanol and 1 cm3 of aqueous 5N sodium hydroxide solution was stirred at a temperature in the region of 70° C. for 21 hours. After cooling to about 20° C., the reaction mass was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 60° C. The residue was taken up in 5 cm3 of a dichloromethane/methanol/aqueous ammonia mixture (40/5/0.5 by volume) and then purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 70-200μ; diameter 1.5 cm; mass 20 g), eluting with a dichloromethane/methanol/aqueous ammonia mixture (40/5/0.5 by volume). The fractions containing the product were combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The foam was taken up in 2 cm3 of methanol, filtered, washed with 1 cm3 of methanol and 2 cm3 of diethyl ether and then oven-dried under reduced pressure (10 kPa) at about 50° C. 0.115 g of 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-[2-(pyridin-2-yloxy)ethyl]piperidine-4-carboxylic acid was obtained in the form of a white solid melting at about 70° C. and becoming sticky.

Workup

  1. temperatureAfter cooling to about 20° C.
  2. concentrationthe reaction mass was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 60° C
  3. custompurified by chromatography under atmospheric pressure, on a column of silica gel (particle size 70-200μ; diameter 1.5 cm; mass 20 g)
  4. washeluting with a dichloromethane/methanol/aqueous ammonia mixture (40/5/0.5 by volume)
  5. additionThe fractions containing the product
  6. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  7. filtrationfiltered
  8. washwashed with 1 cm3 of methanol and 2 cm3 of diethyl ether
  9. customoven-dried under reduced pressure (10 kPa) at about 50° C

Sources & evidence

ORD record
ord-1f5a968a67ea44ba84b6b561425e5685
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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