Sodium Hydroxide → HCID 22470362, compound

HRID 395014Notes

Reaction equation

HRID 395014 reaction equation
[Cl: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:29]([O:31]CC)=[O:30])[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][O:23][C:24]3[S:25][CH:26]=[CH:27][N:28]=3)[CH2:17][CH2:16]1)=[CH:9][C:8]([O:34][CH3:35])=[CH:7][CH:6]=2.[OH-].[Na+]>O1CCOCC1.CO.C(OCC)(=O)C>[Cl: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:29]([OH:31])=[O:30])[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][O:23][C:24]3[S:25][CH:26]=[CH:27][N:28]=3)[CH2:17][CH2:16]1)=[CH:9][C:8]([O:34][CH3:35])=[CH:7][CH:6]=2

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 22468618Ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-[2-(thiazol-2-yloxy)-ethyl]piperidine-4-carboxylate

Product 1

HCID 22470362HCID 22470362, compoundYield 42%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 0.68 g of ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-[2-(thiazol-2-yloxy)-ethyl]piperidine-4-carboxylate in 7 cm3 of dioxane, 9 cm3 of methanol and 2 cm3 of aqueous 5N sodium hydroxide solution was maintained at a temperature in the region of 60° C. for 20 hours. After cooling to about 20° C., the reaction mass was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue obtained was chromatographed under a pressure of 50 kPa of argon, on a column of silica gel (particle size 20-45μ; diameter 2.2 cm; mass 20 g), eluting with a mixture of dichloromethane/methanol (70/30 by volume). The fractions containing the expected product were combined and then concentrated to dryness under the above conditions. The residue obtained was taken up in 5 cm3 of ethyl acetate, stirred for 1 hour at room temperature and then filtered and rinsed with 3 times 3 cm3 of ethyl acetate and then 3 times 3 cm3 of pentane. 0.27 g of 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-[2-(thiazol-2-yloxy)-ethyl]piperidine-4-carboxylic acid was obtained in the form of a white solid melting at 188° C.

Workup

  1. temperatureAfter cooling to about 20° C.
  2. concentrationthe reaction mass was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  3. customThe residue obtained
  4. customwas chromatographed under a pressure of 50 kPa of argon, on a column of silica gel (particle size 20-45μ; diameter 2.2 cm; mass 20 g)
  5. washeluting with a mixture of dichloromethane/methanol (70/30 by volume)
  6. additionThe fractions containing the expected product
  7. concentrationconcentrated to dryness under the above conditions
  8. customThe residue obtained
  9. filtrationfiltered
  10. washrinsed with 3 times 3 cm3 of ethyl acetate

Sources & evidence

ORD record
ord-7966dda332804a42b317065e46c65f55
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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