Sodium Hydroxide → HCID 22470584, compound

HRID 1071264Notes

Reaction equation

HRID 1071264 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH:12]([F:37])[CH2:13][CH2:14][C:15]1([C:32]([O:34]CC)=[O:33])[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][O:23][C:24]3[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=3[F:31])[CH2:17][CH2:16]1)=[CH:9][C:8]([O:38][CH3:39])=[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[CH:12]([F:37])[CH2:13][CH2:14][C:15]1([C:32]([OH:34])=[O:33])[CH2:16][CH2:17][N:18]([CH2:21][CH2:22][O:23][C:24]3[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=3[F:31])[CH2:19][CH2:20]1)=[CH:9][C:8]([O:38][CH3:39])=[CH:7][CH:6]=2

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 22469290HCID 22469290, compound

Product 1

HCID 22470584HCID 22470584, compoundYield 28.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 0.15 g of ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)-3-(R,S)-fluoropropyl]-1-[2-(2,5-difluorophenoxy)ethyl]piperidine-4-carboxylate in 3 cm3 of dioxane, 3 cm3 of methanol and 1 cm3 of aqueous 5N sodium hydroxide solution was maintained at a temperature in the region of 70° C. for 4 hours. After cooling to about 20° C., the reaction mixture was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue was chromatographed under an atmospheric pressure of 60 kPa, on a Bond Elut of 60 cm3 of silica gel (particle size 70-200μ; mass 25 g), eluting with 60 cm3 of a dichloromethane/methanol/aqueous ammonia mixture (40/5/0.5 by volume) and then with a dichloromethane/methanol/aqueous ammonia mixture (40/5/2 by volume). The fractions containing the expected product were combined and then concentrated to dryness according to the same conditions as above. 0.04 g of 4-[3-(3-chloro-6-methoxyquinolin-4-yl)-3-(R,S)-fluoropropyl]-1-[2-(2,5-difluorophenoxy)ethyl]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 reduced pressure (2 kPa) at a temperature in the region of 40° C
  3. customThe residue was chromatographed under an atmospheric pressure of 60 kPa, on a Bond Elut of 60 cm3 of silica gel (particle size 70-200μ; mass 25 g)
  4. washeluting with 60 cm3 of a dichloromethane/methanol/aqueous ammonia mixture (40/5/0.5 by volume)
  5. additionThe fractions containing the expected product
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-774e8547723849b1943ad8bffb6f0ccd
Source dataset
uspto-grants-2005_06
Patent number
US06903217B2

Reaction notes

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