Sodium Hydroxide → HCID 69353295, compound

HRID 2186407Notes

Reaction equation

HRID 2186407 reaction equation
[OH:1][CH:2]([C:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([O:36][CH3:37])[CH:34]=2)[N:29]=[CH:28][CH:27]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]#[C:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[C:15]=2[F:21])[CH2:7][C@@H:6]1[C:22]([O:24]C)=[O:23].[OH-].[Na+]>O1CCOCC1.ClCCl>[OH:1][CH:2]([C:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([O:36][CH3:37])[CH:34]=2)[N:29]=[CH:28][CH:27]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]#[C:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[C:15]=2[F:21])[CH2:7][C@@H:6]1[C:22]([OH:24])=[O:23]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 131723295HCID 131723295, compound

Product 1

HCID 69353295HCID 69353295, compoundYield 59.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 0.810 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(2,3-difluorophenyl)prop-2-ynyl]piperidine-3-carboxylate in 8 cm3 of dioxane to which had been added 1.3 cm3 of 5N aqueous sodium hydroxide solution was stirred for 17 hours at a temperature in the region of 60° C. After cooling to approximately 20° C., the reaction mixture was evaporated under reduced pressure (5 kPa) at a temperature in the region of 50° C. The residue obtained was purified by chromatography under a nitrogen pressure of 50 kPa on a column of silica gel (particle size 20-45 μm; diameter 3 cm; mass 45 g), elution was carried out with a dichloromethane/methanol (92/8 by volume) mixture. A fraction of 275 cm3 was first collected, followed by 20-cm3 fractions. Fractions 12 to 46 were collected. These fractions were combined and concentrated under reduced pressure (5 kPa) at a temperature in the region of 35° C. The residue obtained was taken up in dichloromethane and filtered. The filtrate was evaporated as above and then the new residue obtained was triturated in 10 cm3 of diisopropyl ether. The mixture was stirred for 1 hour at a temperature in the region of 20° C. and then left for 16 hours. The solid precipitate was separated by filtration and washed with 2 times 10 cm3 of the same solvent and then with 2 times 10 cm3 of pentane. 0.47 g of (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(2,3-difluorophenyl)prop-2-ynyl]piperidine-3-carboxylic acid was obtained in the form of a solid with a white color melting at 92° C.

Workup

  1. temperatureAfter cooling to approximately 20° C.
  2. customthe reaction mixture was evaporated under reduced pressure (5 kPa) at a temperature in the region of 50° C
  3. customThe residue obtained
  4. customwas purified by chromatography under a nitrogen pressure of 50 kPa
  5. washon a column of silica gel (particle size 20-45 μm; diameter 3 cm; mass 45 g), elution
  6. customA fraction of 275 cm3 was first collected
  7. customFractions 12 to 46 were collected
  8. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 35° C
  9. customThe residue obtained
  10. filtrationfiltered
  11. customThe filtrate was evaporated as above and then the new residue
  12. customobtained
  13. customwas triturated in 10 cm3 of diisopropyl ether
  14. stirringThe mixture was stirred for 1 hour at a temperature in the region of 20° C.
  15. waitleft for 16 hours
  16. customThe solid precipitate was separated by filtration
  17. washwashed with 2 times 10 cm3 of the same solvent

Sources & evidence

ORD record
ord-08aa0291136144c697539ca1f5d312b7
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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