Triethylamine → HCID 86758146, compound

HRID 2186344Notes

Reaction equation

HRID 2186344 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[CH2:13][CH2:14][CH2:15][C@@H:16]1[CH2:21][CH2:20][N:19]([CH2:22][C:23]#[CH:24])[CH2:18][C@@H:17]1[C:25]([O:27][CH3:28])=[O:26].[F:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1I.C(N(CC)CC)C>C(#N)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[CH2:13][CH2:14][CH2:15][C@@H:16]1[CH2:21][CH2:20][N:19]([CH2:22][C:23]#[C:24][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[F:29])[CH2:18][C@@H:17]1[C:25]([O:27][CH3:28])=[O:26]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 676731-Fluoro-2-iodobenzeneHCID 86758147HCID 86758147, compound

Product 1

HCID 86758146HCID 86758146, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
20 °C

Procedure

0.041 g of tetrakis(triphenylphosphine)palladium and 0.070 g of cuprous iodide were added, at a temperature in the region of 20° C. and under an inert atmosphere, to a stirred solution of 0.7 g of methyl (3R,4R)-4-[3-(6-methoxyquinolin-4-yl)propyl]-1-(prop-2-ynyl)piperidine-3-carboxylate in 14 cm3 of acetonitrile. 0.32 cm3 of 1-fluoro-2-iodobenzene and 0.51 cm3 of triethylamine were subsequently added. The mixture was stirred at a temperature in the region of 20° C. for 20 hours. The reaction mixture was filtered and the cake was washed with 3 times 10 cm3 of acetonitrile. The combined filtrates were taken up with stirring in a mixture of 100 cm3 of dichloromethane and 100 cm3 of water. The organic phase was separated by settling, washed with 3 times 50 cm3 of a saturated sodium chloride solution, dried over magnesium sulfate, and then, after filtration, concentrated under reduced pressure (2 kPa) at a temperature in the region of 35° C. The residue obtained was purified by chromatography under argon pressure (50 kPa) on a column of silica gel (particle size 40-63 μm; diameter 4 cm; height 14 cm), elution was carried out with ethyl acetate, and 2-cm3 fractions were collected. Fractions 33 to 160 were combined and then evaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.56 g of methyl (3R,4R)-4-(3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(2-fluorophenyl)prop-2-ynyl]piperidine-3-carboxylate was obtained in the form of an oil with a light brown color.

Workup

  1. filtrationThe reaction mixture was filtered
  2. washthe cake was washed with 3 times 10 cm3 of acetonitrile
  3. stirringwith stirring in a mixture of 100 cm3 of dichloromethane and 100 cm3 of water
  4. customThe organic phase was separated
  5. washwashed with 3 times 50 cm3 of a saturated sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. filtrationafter filtration
  8. concentrationconcentrated under reduced pressure (2 kPa) at a temperature in the region of 35° C
  9. customThe residue obtained
  10. customwas purified by chromatography under argon pressure (50 kPa)
  11. washon a column of silica gel (particle size 40-63 μm; diameter 4 cm; height 14 cm), elution
  12. customwere collected
  13. customevaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-fb72df8c0c0642b8829fbeff1cea4eef
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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