Sodium Hydroxide → HCID 22469516, compound

HRID 394997Notes

Reaction equation

HRID 394997 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:35]=[CH:36][C:37]=1[F:38])[O:5][CH2:6][CH2:7][N:8]1[CH2:13][CH2:12][C:11]([CH2:19][CH2:20][CH2:21][C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[C:29]([O:32][CH3:33])[CH:30]=3)[N:25]=[CH:24][C:23]=2[F:34])([C:14]([O:16]CC)=[O:15])[CH2:10][CH2:9]1.[OH-].[Na+]>O1CCOCC1.CO>[F:1][C:2]1[CH:3]=[C:4]([CH:35]=[CH:36][C:37]=1[F:38])[O:5][CH2:6][CH2:7][N:8]1[CH2:9][CH2:10][C:11]([CH2:19][CH2:20][CH2:21][C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[C:29]([O:32][CH3:33])[CH:30]=3)[N:25]=[CH:24][C:23]=2[F:34])([C:14]([OH:16])=[O:15])[CH2:12][CH2:13]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 22470642HCID 22470642, compound

Product 1

HCID 22469516HCID 22469516, compoundYield 83.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 0.38 g of ethyl 1-[2-(3,4-difluorophenoxy)ethyl]-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate in 3 cm3 of dioxane, 3 cm3 of methanol and 2.1 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 mixture of dichloromethane/methanol/aqueous ammonia (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-(3,4-difluoro-phenoxy)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 mixture of dichloromethane/methanol/aqueous ammonia (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-d621f0d04fff4484a587076902760731
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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