Sodium Hydroxide → HCID 69353128, compound

HRID 2186403Notes

Reaction equation

HRID 2186403 reaction equation
[OH-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][CH:9]=[C:8]2[CH2:15][CH2:16][CH2:17][C@@H:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25]#[C:26][C:27]2[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([F:34])[CH:28]=2)[CH2:20][C@@H:19]1[CH2:35][C:36]([O:38]C)=[O:37]>O1CCOCC1.O.C(OCC)C>[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][CH:9]=[C:8]2[CH2:15][CH2:16][CH2:17][C@@H:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25]#[C:26][C:27]2[CH:28]=[C:29]([F:34])[CH:30]=[C:31]([F:33])[CH:32]=2)[CH2:20][C@@H:19]1[CH2:35][C:36]([OH:38])=[O:37]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 86758170HCID 86758170, compound

Product 1

HCID 69353128HCID 69353128, compoundYield 88.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

0.83 cm3 of 5N aqueous sodium hydroxide solution was introduced with stirring, at a temperature in the region of 20° C., into a solution of 0.525 g of methyl (3R,4R)-4-[3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(3,5-difluorophenyl)prop-2-ynyl]piperidine-3-acetate in 5 cm3 of dioxane and then the mixture was heated for 3 hours at a temperature in the region of 60° C. After cooling to approximately 20° C., the mixture was stirred for 3 days and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was taken up in 15 cm3 of water and then the solution was extracted with 5 cm3 of ethyl acetate. The aqueous phase was brought to a pH in the region of 5-6 by addition of 4.1 cm3 of 1N aqueous hydrochloric acid and then extracted, first with 30 cm3 of dichloromethane and then with 10 cm3 of the same solvent. The organic extracts were combined, washed with 2 times 5 cm3 of water, dried over magnesium sulfate, filtered, and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was taken up in diethyl ether and then concentrated under the same conditions as above until a constant weight was obtained. 0.45 g of (3R,4R)-4-[3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(3,5-difluorophenyl)prop-2-ynyl]piperidine-3-acetic acid was obtained in the form of a solid with a light beige color.

Workup

  1. temperatureAfter cooling to approximately 20° C.
  2. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  3. customThe residue obtained
  4. extractionthe solution was extracted with 5 cm3 of ethyl acetate
  5. additionThe aqueous phase was brought to a pH in the region of 5-6 by addition of 4.1 cm3 of 1N aqueous hydrochloric acid
  6. extractionextracted, first with 30 cm3 of dichloromethane
  7. washwashed with 2 times 5 cm3 of water
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  11. customThe residue obtained
  12. concentrationconcentrated under the same conditions as above until a constant weight
  13. customwas obtained

Sources & evidence

ORD record
ord-75db454e1d1940aea5a7ef231859a9c0
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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