Triethylamine → Ethyl 4-((5-chloro-6-cyanopyridin-3-yl)ethynyl)-3-methylbenzoate

HRID 340288Notes

Reaction equation

HRID 340288 reaction equation
[Cl:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[C:6](Cl)[CH:7]=1.[C:11]([C:13]1[CH:23]=[CH:22][C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:15][C:14]=1[CH3:24])#[CH:12].C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C.[OH-].[NH4+].[Cu]I>[Cl:1][C:2]1[CH:7]=[C:6]([C:12]#[C:11][C:13]2[CH:23]=[CH:22][C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:15][C:14]=2[CH3:24])[CH:5]=[N:4][C:3]=1[C:9]#[N:10]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 27696993,5-Dichloro-2-cyanopyridineHCID 86652354Ethyl 4-ethynyl-3-methylbenzoate

Product 1

HCID 66875033Ethyl 4-((5-chloro-6-cyanopyridin-3-yl)ethynyl)-3-methylbenzoate

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 14923Ammonium HydroxideSolvent

Procedure

A solution of 3,5-dichloropicolinonitrile (1.0 eq.), ethyl 4-ethynyl-3-methylbenzoate (from the previous step) (1.0 eq.), trans-dichlororbis(triphenylphosphine)palladium (II) (10 mol %), copper (I) iodide (20 mol %), and triethylamine (5.0 eq.) in DMF (0.3 M) was stirred at 50° C. for 3 hours. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate and 10% aqueous ammonium hydroxide. The two phases were separated, and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-10% ethyl acetate in hexane to give ethyl 4-((5-chloro-6-cyanopyridin-3-yl)ethynyl)-3-methylbenzoate as a white solid.

Workup

  1. customThe two phases were separated
  2. extractionthe aqueous layer was extracted twice with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated en vacuo
  6. customThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record
ord-282376152ded4828a5c6b09e11f44c64
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Reaction notes

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