Potassium Iodide → methyl (3R,4R)-4-[3-oxo-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylsulfanyl)ethyl]piperidine-3-carboxylate

HRID 1767097Notes

Reaction equation

HRID 1767097 reaction equation
[O:1]=[C:2]([C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([O:25][CH3:26])[CH:23]=2)[N:18]=[CH:17][C:16]=1[F:27])[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][NH:8][CH2:7][C@@H:6]1[C:11]([O:13][CH3:14])=[O:12].Br[CH2:29][CH2:30][S:31][C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=1[F:39].[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[O:1]=[C:2]([C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([O:25][CH3:26])[CH:23]=2)[N:18]=[CH:17][C:16]=1[F:27])[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:29][CH2:30][S:31][C:32]2[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=2[F:39])[CH2:7][C@@H:6]1[C:11]([O:13][CH3:14])=[O:12]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 11501661methyl (3R,4R)-4-[3-oxo-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylateHCID 115216692-(2-bromoethylsulfanyl)-1,4-difluorobenzene

Product 1

HCID 86592161methyl (3R,4R)-4-[3-oxo-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylsulfanyl)ethyl]piperidine-3-carboxylateYield 48.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 0.57 g of methyl (3R,4R)-4-[3-oxo-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate obtained as described in example 1, 0.462 g of 2-(2-bromoethylsulfanyl)-1,4-difluorobenzene, 0.253 g of potassium iodide and 1.05 g of potassium carbonate in 25 cm3 of acetonitrile is heated with stirring and under an inert atmosphere for 20 hours at a temperature in the region of 75° C. After cooling to a temperature in the region of 20° C., the reaction medium is filtered and the insoluble material is washed with 2 times 10 cm3 of acetonitrile. The filtrate is evaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C. The evaporation residue is taken up with 50 cm3 of distilled water and 100 cm3 of ethyl acetate. The organic phase is washed with 3 times 30 cm3 of distilled water and 2 times 50 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulfate and evaporated according to the conditions mentioned above. The oil obtained is purified by chromatography on a column of silica gel (particle size 70–200 μm; diameter 2.5 cm), eluting with a mixture of dichloromethane-methanol (9/10 by volume) and collecting fractions of 10 cm3. The fractions containing the expected product are pooled and then evaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.4 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 the form of an orange-colored viscous oil, is obtained.

Workup

  1. customobtained
  2. temperatureis heated
  3. temperatureAfter cooling to a temperature in the region of 20° C.
  4. filtrationthe reaction medium is filtered
  5. washthe insoluble material is washed with 2 times 10 cm3 of acetonitrile
  6. customThe filtrate is evaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C
  7. washThe organic phase is washed with 3 times 30 cm3 of distilled water and 2 times 50 cm3 of a saturated aqueous sodium chloride solution
  8. dry with materialdried over magnesium sulfate
  9. customevaporated
  10. customThe oil obtained
  11. customis purified by chromatography on a column of silica gel (particle size 70–200 μm; diameter 2.5 cm)
  12. washeluting with a mixture of dichloromethane-methanol (9/10 by volume)
  13. customcollecting fractions of 10 cm3
  14. additionThe fractions containing the expected product
  15. customevaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-8053d0c7cb8f496da9c535d5931f73a8
Source dataset
uspto-grants-2007_06
Patent number
US07232834B2

Reaction notes

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