5-Bromonicotinonitrile → Tert-butyl 4-[3-(5-cyanopyridin-3-yl)prop-2-ynylidene]piperidine-1-carboxylate

HRID 1895966Notes

Reaction equation

HRID 1895966 reaction equation
[CH:1](=[C:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1)[C:2]#[CH:3].Br[C:18]1[CH:19]=[N:20][CH:21]=[C:22]([CH:25]=1)[C:23]#[N:24]>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>[C:23]([C:22]1[CH:25]=[C:18]([C:3]#[C:2][CH:1]=[C:4]2[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]2)[CH:19]=[N:20][CH:21]=1)#[N:24]

Participants

5

Reactant 2

HCID 7367935-BromonicotinonitrileHCID 86661548tert-Butyl 4-(prop-2-yn-1-ylidene)piperidine-1-carboxylate

Product 1

HCID 25183829Tert-butyl 4-[3-(5-cyanopyridin-3-yl)prop-2-ynylidene]piperidine-1-carboxylateYield 100%

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 2b (0.5 g, 2.26 mmol), 5-bromonicotinonitrile (0.511 g, 2.26 mmol), bis(triphenylphosphine)palladium(II)dichloride (80 mg, 0.05 mmol), CuI (43.1 mg, 0.1 mmol) in anhydrous and degassed triethylamine (12.6 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 gradient from 4:96 to 30:70) affording the title product (0.731 g).

Workup

  1. customdegassed triethylamine (12.6 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 gradient from 4:96 to 30:70)

Sources & evidence

ORD record
ord-42c85cdf19894ecebce7f923b5165288
Source dataset
uspto-grants-2013_08
Patent number
US08518916B2

Reaction notes

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