Sodium Hydroxide → (3R,4R)-4-[3-oxo-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylsulfanyl)ethyl]piperidine-3-carboxylic acid

HRID 1767096Notes

Reaction equation

HRID 1767096 reaction equation
[O:1]=[C: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][C:27]=1[F:38])[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][S:13][C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[F:21])[CH2:7][C@@H:6]1[C:22]([O:24]C)=[O:23].[OH-].[Na+]>Cl>[O:1]=[C: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][C:27]=1[F:38])[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][S:13][C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[F:21])[CH2:7][C@@H:6]1[C:22]([OH:24])=[O:23]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86592161methyl (3R,4R)-4-[3-oxo-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylsulfanyl)ethyl]piperidine-3-carboxylate

Product 1

HCID 69346139(3R,4R)-4-[3-oxo-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylsulfanyl)ethyl]piperidine-3-carboxylic acidYield 73.9%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
20 °C

Procedure

A mixture of 0.1 g of methyl (3R,4R)-4-[3-oxo-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylsulfanyl)ethyl]piperidine-3-carboxylate in 2 cm3 of 5N hydrochloric acid is brought to a temperature in the region of 80° C. with stirring and under an inert atmosphere for 5 hours. After cooling to around 20° C., the reaction medium is neutralized with 1.8 cm3 of 5N sodium hydroxide until a pH of 6 is obtained, and is then extracted with 20 cm3 of dichloromethane. The organic phase is dried over magnesium sulfate, filtered, and then evaporated to dryness under reduced pressure (2 kPa) at a temperature in the region of 30° C. The residue obtained is purified by chromatography on a column of silica gel (particle size 70–200 μm; diameter 2 cm), eluting with a mixture of dichloromethane-methanol-aqueous ammonia (28%) (40/5/0.5 by volume) and collecting fractions of 10 cm3. The fractions containing the expected product are pooled and then evaporated according to the conditions described above. 0.072 g of (3R,4R)-4-[3-oxo-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylsulfanyl)ethyl]piperidine-3-carboxylic acid, in the form of a beige-colored solid, is obtained.

Workup

  1. customis brought to a temperature in the region of 80° C.
  2. customis obtained
  3. extractionis then extracted with 20 cm3 of dichloromethane
  4. dry with materialThe organic phase is dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness under reduced pressure (2 kPa) at a temperature in the region of 30° C
  7. customThe residue obtained
  8. customis purified by chromatography on a column of silica gel (particle size 70–200 μm; diameter 2 cm)
  9. washeluting with a mixture of dichloromethane-methanol-aqueous ammonia (28%) (40/5/0.5 by volume)
  10. customcollecting fractions of 10 cm3
  11. additionThe fractions containing the expected product
  12. customevaporated

Sources & evidence

ORD record
ord-15e7212e57b84a698b19141cf754f0dd
Source dataset
uspto-grants-2007_06
Patent number
US07232834B2

Reaction notes

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