Triethylamine → 2-Fluoro-3-[2-(4-fluoro-2-nitrophenyl)ethynyl]pyridine

HRID 75188Notes

Reaction equation

HRID 75188 reaction equation
[C:1]([C:3]1[C:4]([F:9])=[N:5][CH:6]=[CH:7][CH:8]=1)#[CH:2].[F:10][C:11]1[CH:16]=[CH:15][C:14](I)=[C:13]([N+:18]([O-:20])=[O:19])[CH:12]=1.C(N(CC)CC)C>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[F:9][C:4]1[C:3]([C:1]#[C:2][C:14]2[CH:15]=[CH:16][C:11]([F:10])=[CH:12][C:13]=2[N+:18]([O-:20])=[O:19])=[CH:8][CH:7]=[CH:6][N:5]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 27373475-Fluoro-2-iodonitrobenzeneHCID 569723573-Ethynyl-2-fluoropyridine

Product 1

HCID 668866782-Fluoro-3-[2-(4-fluoro-2-nitrophenyl)ethynyl]pyridineYield 85.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

Into a round bottom flask was added 3-ethynyl-2-fluoropyridine (0.3 g, 0.002 mol), 4-fluoro-1-iodo-2-nitrobenzene (0.675 g, 0.00253 mol), bis(triphenylphosphine)palladium(II) chloride (0.09 g, 0.1 mmol), copper(I) iodide (0.04 g, 0.2 mmol), and triethylamine (0.52 mL, 3.7 mmol) in N,N-dimethylformamide (4 mL). The reaction was stirred at room temperature for 2 hours. The reaction was extracted with ethyl acetate, and the combined organic extracts were washed with brine (3×), dried over MgSO4, and purified by column chromatography on silica gel (10% ethyl acetate 90% hexanes), to give 0.443 g of product. 1H NMR (400 MHz, CDCl3): δ 8.44-8.50 (m, 1H), 7.99-8.02 (m, 1H), 7.79-7.90 (m, 1H), 7.78-7.82 (m, 1H), 7.37-7.42 (m, 1H), 7.23-7.29 (m, 1H). MS [M+H]=261.0.

Workup

  1. extractionThe reaction was extracted with ethyl acetate
  2. washthe combined organic extracts were washed with brine (3×)
  3. dry with materialdried over MgSO4
  4. custompurified by column chromatography on silica gel (10% ethyl acetate 90% hexanes)

Sources & evidence

ORD record
ord-a8dcd032f7894729a49e8084a75eb9b5
Source dataset
uspto-grants-2014_09
Patent number
US08835423B2

Reaction notes

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