Potassium Iodide → methyl (3R,4R)-1-[2-(3,5-difluorophenylthio)ethyl]-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate

HRID 2186405Notes

Reaction equation

HRID 2186405 reaction equation
C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Br[CH2:10][CH2:11][S:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[C:15]([F:20])[CH:14]=1.[OH:21][CH:22]([C:35]1[C:44]2[C:39](=[CH:40][CH:41]=[C:42]([O:45][CH3:46])[CH:43]=2)[N:38]=[CH:37][CH:36]=1)[CH2:23][CH2:24][C@@H:25]1[CH2:30][CH2:29][NH:28][CH2:27][C@@H:26]1[C:31]([O:33][CH3:34])=[O:32]>C(#N)C.CO>[F:20][C:15]1[CH:14]=[C:13]([S:12][CH2:11][CH2:10][N:28]2[CH2:29][CH2:30][C@@H:25]([CH2:24][CH2:23][CH:22]([OH:21])[C:35]3[C:44]4[C:39](=[CH:40][CH:41]=[C:42]([O:45][CH3:46])[CH:43]=4)[N:38]=[CH:37][CH:36]=3)[C@@H:26]([C:31]([O:33][CH3:34])=[O:32])[CH2:27]2)[CH:18]=[C:17]([F:19])[CH:16]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 224542321-[(2-Bromoethyl)thio]-3,5-difluorobenzeneHCID 66688355HCID 66688355, compound

Product 1

HCID 131723294methyl (3R,4R)-1-[2-(3,5-difluorophenylthio)ethyl]-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylateYield 44.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
80 °C

Procedure

0.332 g of potassium carbonate, then 0.4 g of potassium iodide and, finally, 0.675 g of 1-[(2-bromoethyl)thio]-3,5-difluorobenzene, dissolved beforehand in 5 cm3 of acetonitrile, were added at a temperature in the region of 20° C., with stirring and under an inert atmosphere, to a solution of 0.717 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate in 15 cm3 of acetonitrile and 1 cm3 of methanol. The mixture was heated for 3 hours at a temperature in the region of 80° C. After cooling to a temperature in the region of 20° C., the reaction mixture was filtered and the cake was washed with 2 times 5 cm3 of acetonitrile. The filtrate was evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography under a nitrogen pressure of 50 kPa on a column of silica gel (particle size 40-63 μm; diameter 3.5 cm; height 35 cm), elution was carried out with a dichloromethane/methanol (95/5 by volume) mixture, and 35-cm3 fractions were collected. Fractions 18 to 21 were combined and then evaporated as above. 0.47 g of methyl (3R,4R)-1-[2-(3,5-difluorophenylthio)ethyl]-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate was obtained in the form of a viscous oil with an orange-yellow color.

Workup

  1. additionwere added at a temperature in the region of 20° C.
  2. temperatureAfter cooling to a temperature in the region of 20° C.
  3. filtrationthe reaction mixture was filtered
  4. washthe cake was washed with 2 times 5 cm3 of acetonitrile
  5. customThe filtrate was evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  6. customThe residue obtained
  7. customwas purified by chromatography under a nitrogen pressure of 50 kPa
  8. washon a column of silica gel (particle size 40-63 μm; diameter 3.5 cm; height 35 cm), elution
  9. customwere collected
  10. customevaporated as above

Sources & evidence

ORD record
ord-929677dbe8ee493baba541c341fa92cf
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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