Sodium Hydroxide → HCID 22468924, compound

HRID 394996Notes

Reaction equation

HRID 394996 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:30]([O:32]CC)=[O:31])[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][S:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:17][CH2:16]1)=[CH:9][C:8]([O:35][CH3:36])=[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:30]([OH:32])=[O:31])[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][S:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=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 22468840HCID 22468840, compound

Product 1

HCID 22468924HCID 22468924, compoundYield 81.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 0.39 g of ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-(2-phenylthioethyl)piperidine-4-carboxylate in 3 cm3 of dioxane, 3 cm3 of methanol and 2.3 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 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-(2-phenylthioethyl)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-999f4e8302784688b80ee83d247f9315
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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