Triethylamine → 4-Pyridin-2-ylethynyl-quinoline-2-carboxylic Acid Ethyl Ester

HRID 8217

Reaction equation

HRID 8217 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:3]=1.C(N(CC)CC)C.[C:24]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1)#[CH:25]>CC#N.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>[CH2:15]([O:14][C:12]([C:4]1[CH:3]=[C:2]([C:25]#[C:24][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=1)=[O:13])[CH3:16]

Participants

7

Reactant 3

HCID 8471Triethylamine2×HCID 137268EthynylpyridineHCID 21992780Ethyl 4-bromoquinoline-2-carboxylate

Product 1

HCID 693649014-Pyridin-2-ylethynyl-quinoline-2-carboxylic Acid Ethyl EsterYield 50.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalyst2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
77.5 °C

Procedure

A mixture of ethyl 4-bromoquinoline-2-carboxylate (2.80 g, 10.0 mmol, J. Org. Chem. 1947, 12, 456), triethylamine (1.7 mL, 12 mmol), bis(triphenylphosphine)-palladium(II)chloride (0.561 g, 0.80 mmol), CuI (0.114 g, 0.60 mmol), and 2-ethynylpyridine (1.11 g, 10.8 mmol) in CH3CN (80 mL) is heated at 75-80° C. for 18 h in a sealed tube. Additional triethylamine (0.85 ml, 6.1 mmol), bis(triphenylphosphine)palladium (II) chloride (0.23 g, 0.40 mmol), and CuI (0.055 g, 0.29 mmol) is added and the mixture heated for an additional 18 h. The mixture is concentrated in vacuo and partitioned between water and chloroform. The chloroform extracts are washed with brine and evaporated. The residue is chromatographed on SiO2 (50% ethyl acetate/hexanes) to yield 1.52 g (50%) of a yellow solid. Precipitation from ethyl acetate gave the title compound as yellow crystals: mp 129-131° C.; MS ES+ m/e 303 (M+1).

Workup

  1. temperaturethe mixture heated for an additional 18 h
  2. concentrationThe mixture is concentrated in vacuo
  3. custompartitioned between water and chloroform
  4. washThe chloroform extracts are washed with brine
  5. customevaporated
  6. customThe residue is chromatographed on SiO2 (50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9dbb6f48418e4ea8ad11976c7e04ceca
Source dataset
uspto-grants-2006_08
Patent number
US07087626B2

Linked notes

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