Sodium Hydroxide → HCID 22468730, compound

HRID 394995Notes

Reaction equation

HRID 394995 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[S:9][CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][C:15]([CH2:23][CH2:24][CH2:25][C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[C:33]([O:36][CH3:37])[CH:34]=3)[N:29]=[CH:28][C:27]=2[F:38])([C:18]([O:20]CC)=[O:19])[CH2:14][CH2:13]1.[OH-].[Na+]>O1CCOCC1.CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[S:9][CH2:10][CH2:11][N:12]1[CH2:13][CH2:14][C:15]([CH2:23][CH2:24][CH2:25][C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[C:33]([O:36][CH3:37])[CH:34]=3)[N:29]=[CH:28][C:27]=2[F:38])([C:18]([OH:20])=[O:19])[CH2:16][CH2:17]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 22469503HCID 22469503, compound

Product 1

HCID 22468730HCID 22468730, compoundYield 121.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 0.26 g of ethyl 1-[2-(2,5-difluorophenylthio)ethyl]-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate in 3 cm3 of dioxane, 3 cm3 of methanol and 1.4 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-(2,5-difluorophenylthio)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-e32433e0ac584aed99c3fbafd04a1467
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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