Sodium Hydroxide → HCID 22470915, compound

HRID 394999Notes

Reaction equation

HRID 394999 reaction equation
[F:1][C:2]1[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:3]=1[O:4][CH2:5][CH2:6][N:7]1[CH2:12][CH2:11][C:10]([CH2:18][CH2:19][CH2:20][C:21]2[C:30]3[C:25](=[CH:26][CH:27]=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][C:22]=2[F:33])([C:13]([O:15]CC)=[O:14])[CH2:9][CH2:8]1.[OH-].[Na+]>O1CCOCC1.CO>[F:38][C:34]1[CH:35]=[CH:36][CH:37]=[C:2]([F:1])[C:3]=1[O:4][CH2:5][CH2:6][N:7]1[CH2:8][CH2:9][C:10]([CH2:18][CH2:19][CH2:20][C:21]2[C:30]3[C:25](=[CH:26][CH:27]=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][C:22]=2[F:33])([C:13]([OH:15])=[O:14])[CH2:11][CH2:12]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 22471327HCID 22471327, compound

Product 1

HCID 22470915HCID 22470915, compoundYield 81.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 0.39 g of ethyl 1-[2-(2,6-difluorophenoxy)ethyl]-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate in 3 cm3 of dioxane, 3 cm3 of methanol and 2.2 cm3 of aqueous 5N sodium hydroxide solution was stirred at a temperature in the region of 70° C. for 17 hours. After cooling to about 20° C., the reaction mixture was concentrated to dryness under a pressure gradually reduced from 30 kPa to 2.5 kPa and at a temperature in the region of 45° C. The residue was taken up in 5 cm3 of a dichloromethane/methanol/aqueous ammonia mixture (40/5/0.5 by volume) and was then purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 10 g), eluting with a dichloromethane/methanol/aqueous ammonia mixture (90/9/0.9 by volume) and then with a chloroform/methanol/aqueous ammonia mixture (77.5/19.5/3). The fractions containing the product were combined, concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. and dried in a desiccator (10 kPa). 0.3 g of 1-[2-(2,6-difluorophenoxy)ethyl]-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylic acid was obtained in the form of a white solid.

Workup

  1. temperatureAfter cooling to about 20° C.
  2. concentrationthe reaction mixture was concentrated to dryness under a pressure
  3. customgradually reduced from 30 kPa to 2.5 kPa and at a temperature in the region of 45° C
  4. customwas then purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 10 g)
  5. washeluting with a dichloromethane/methanol/aqueous ammonia mixture (90/9/0.9 by volume)
  6. additionThe fractions containing the product
  7. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C.
  8. customdried in a desiccator (10 kPa)

Sources & evidence

ORD record
ord-a66b5edd23014674b282f601845dde7f
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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