4-Bromo-2,6-difluoroanisole → 2-(4-(3-(3,5-Difluoro-4-methoxyphenyl)prop-2-yn-1-ylidene)piperidin-1-yl)-3-nitropyridine

HRID 1895979Notes

Reaction equation

HRID 1895979 reaction equation
[N+:1]([C:4]1[C:5]([N:10]2[CH2:15][CH2:14][C:13](=[CH:16][C:17]#[CH:18])[CH2:12][CH2:11]2)=[N:6][CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].Br[C:20]1[CH:25]=[C:24]([F:26])[C:23]([O:27][CH3:28])=[C:22]([F:29])[CH:21]=1>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[F:26][C:24]1[CH:25]=[C:20]([C:18]#[C:17][CH:16]=[C:13]2[CH2:14][CH2:15][N:10]([C:5]3[C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=[CH:7][N:6]=3)[CH2:11][CH2:12]2)[CH:21]=[C:22]([F:29])[C:23]=1[O:27][CH3:28]

Participants

5

Reactant 2

HCID 27732874-Bromo-2,6-difluoroanisoleHCID 866273353-Nitro-2-(4-prop-2-ynylidenepiperidin-1-yl)pyridine

Product 1

HCID 866273392-(4-(3-(3,5-Difluoro-4-methoxyphenyl)prop-2-yn-1-ylidene)piperidin-1-yl)-3-nitropyridineYield 27.7%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
80 °C

Procedure

A mixture of Compound 1c (50 mg, 0.206 mmol), 4-bromo-2,6-difluoroanisole (45.9 mL, 0.206 mmol), bis(triphenylphosphine)palladium(II)dichloride (7.23 mg, 0.012 mmol), CuI (3.92 mg, 0.206 mmol) in anhydrous and degassed triethylamine (3 mL) was heated at 80° C. under a nitrogen atmosphere for 2 h in a sealed vessel. The reaction mixture was cooled, filtered on Celite, poured into water and extracted with EtOAc. The combined organic layers were washed with brine, dried on Na2SO4 and evaporated to dryness in vacuo to afford a residue, which was purified by flash chromatography (EtOAc—Petroleum Ether 10:90) affording the title product (22 mg).

Workup

  1. customdegassed triethylamine (3 mL)
  2. temperatureThe reaction mixture was cooled
  3. filtrationfiltered on Celite
  4. additionpoured into water
  5. extractionextracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. customdried on Na2SO4
  8. customevaporated to dryness in vacuo
  9. customto afford a residue, which
  10. customwas purified by flash chromatography (EtOAc—Petroleum Ether 10:90)

Sources & evidence

ORD record
ord-fc3d88a971a54ff5addcf22fcd08caeb
Source dataset
uspto-grants-2013_08
Patent number
US08518916B2

Reaction notes

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