Hydrochloric Acid → (3Rs,4rs)-4-[3-(r,s)-amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-3-acetic acid hydrochloride

HRID 394712Notes

Reaction equation

HRID 394712 reaction equation
[NH2:1][CH:2]([C:27]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([O:37][CH3:38])[CH:35]=2)[N:30]=[CH:29][C:28]=1[F:39])[CH2:3][CH2:4][CH: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][CH:6]1[CH2:22][C:23]([O:25]C)=[O:24].[OH-].[Na+].O1CCOCC1.[ClH:48]>O.CC(C)=O>[ClH:48].[NH2:1][CH:2]([C:27]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([O:37][CH3:38])[CH:35]=2)[N:30]=[CH:29][C:28]=1[F:39])[CH2:3][CH2:4][CH: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][CH:6]1[CH2:22][C:23]([OH:25])=[O:24]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 131724013Methyl (3rs,4rs)-4-[3-(r,s)-amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-3-acetate

Product 1

HCID 69901151(3Rs,4rs)-4-[3-(r,s)-amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-3-acetic acid hydrochloride

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of 0.09 g of methyl (3RS,4RS)-4-[3-(R,S)-amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-3-acetate in 0.36-cm3 of a 1 N aqueous sodium hydroxide solution and 3-cm3 of dioxane was heated at a temperature in the region of 55° C., with stirring and under an inert atmosphere, for 4 hours. After cooling in the vicinity of 20° C., the reaction mixture was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 50° C. The evaporation residue obtained was taken up in 5-cm3 of distilled water and acidified with a 1-N aqueous hydrochloric acid solution and was concentrated. The aqueous phase was washed with 8-cm3 of dichloromethane and then concentrated according to the conditions described above. The residue obtained was taken up in 10-cm3 of acetone and then it was filtered on sintered glass. 0.081 g of (3RS,4RS)-4-[3-(R,S)-amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-3-acetic acid hydrochloride wereobtained in the form of a white solid.

Workup

  1. temperatureAfter cooling in the vicinity of 20° C.
  2. concentrationthe reaction mixture was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 50° C
  3. customThe evaporation residue obtained
  4. concentrationwas concentrated
  5. washThe aqueous phase was washed with 8-cm3 of dichloromethane
  6. concentrationconcentrated
  7. customThe residue obtained
  8. filtrationit was filtered on sintered glass

Sources & evidence

ORD record
ord-76c132a5c50e47f2a9d43d701f4de960
Source dataset
uspto-grants-2003_08
Patent number
US06602884B2

Reaction notes

Loading…