Sodium Hydroxide → (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(5-chlorothien-2-yl)ethyl]piperidine-3-carboxylic acid

HRID 2186375Notes

Reaction equation

HRID 2186375 reaction equation
[OH:1][CH:2]([C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[C:30]([O:33][CH3:34])[CH:31]=2)[N:26]=[CH:25][CH:24]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][C:13]2[S:14][C:15]([Cl:18])=[CH:16][CH:17]=2)[CH2:7][C@@H:6]1[C:19]([O:21]C)=[O:20].[OH-].[Na+]>O1CCOCC1>[OH:1][CH:2]([C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[C:30]([O:33][CH3:34])[CH:31]=2)[N:26]=[CH:25][CH:24]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][C:13]2[S:14][C:15]([Cl:18])=[CH:16][CH:17]=2)[CH2:7][C@@H:6]1[C:19]([OH:21])=[O:20]

Participants

4

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 131723280methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(5-chlorothien-2-yl)ethyl]piperidine-3-carboxylate

Product 1

HCID 70174904(3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(5-chlorothien-2-yl)ethyl]piperidine-3-carboxylic acidYield 67.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 0.460 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(5-chlorothien-2-yl)ethyl]piperidine-3-carboxylate in 5 cm3 of dioxane which had been added 0.51 cm3 of a 5N aqueous sodium hydroxide solution was stirred at a temperature in the region of 60° C. for 48 hours. After a further addition of 1 cm3 of 5N sodium hydroxide solution, the mixture was again heated at a temperature in the region of 70° C. for 72 hours. The reaction mixture was evaporated under reduced pressure (5 kPa) at a temperature in the region of 45° C. and then the residue obtained was purified by chromatography under a nitrogen pressure of 40 kPa on a column of silica gel (particle size 40-63 μm; diameter 3 cm; silica height 27 cm), elution was carried out with a dichloromethane/methanol/28% aqueous ammonia (14/4/0.6 by volume) mixture, and 15-cm3 fractions were collected. Fractions 7 to 16 were evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. 0.30 g of (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(5-chlorothien-2-yl)ethyl]piperidine-3-carboxylic acid was obtained in the form of a foam with a white color.

Workup

  1. temperaturethe mixture was again heated at a temperature in the region of 70° C. for 72 hours
  2. customThe reaction mixture was evaporated under reduced pressure (5 kPa) at a temperature in the region of 45° C.
  3. customthe residue obtained
  4. customwas purified by chromatography under a nitrogen pressure of 40 kPa
  5. washon a column of silica gel (particle size 40-63 μm; diameter 3 cm; silica height 27 cm), elution
  6. customwere collected
  7. customFractions 7 to 16 were evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-ca779b6f9764419fb3776c1ec13a4c54
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

Loading…