Tetrahydrofuran → HCID 66570997, compound

HRID 1619282Notes

Reaction equation

HRID 1619282 reaction equation
[C:1]([N:5]([CH3:20])[C:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]#[C:15][Si](C)(C)C)=[CH:10][N:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24](I)[CH:23]=1.CCN(CC)CC.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>CN(C=O)C.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:1]([N:5]([CH3:20])[C:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]#[C:15][C:24]2[CH:25]=[CH:26][CH:27]=[C:22]([F:21])[CH:23]=2)=[CH:10][N:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 707251-Fluoro-3-iodobenzeneHCID 2724141Tetrabutylammonium FluorideHCID 70896636HCID 70896636, compound

Product 1

HCID 66570997HCID 66570997, compoundYield 103.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

5-Trimethylsilanylethynyl-pyridine-2-carboxylic acid tert-butyl-methyl-amide (Example 3, step 2) (60 mg, 0.2 mmol) was dissolved in DMF (1 ml). 1-Fluoro-3-iodobenzene (74 mg, 0.33 mmol, 1.6 equiv.), Et3N (87 μl, 0.62 mmol, 3 equiv.), Bis-(triphenylphosphine)-palladium(II)dichloride (7 mg, 10.4 μmol, 0.05 equiv.) and copper(I)iodide (0.4 mg, 2 μmol, 0.01 equiv.) were added under nitrogen and the mixture was heated to 70° C. TBAF 1M in THF (230 μl, 0.23 mmol, 1.1 equiv.) was added dropwise over a period of 20 minutes at 70° C. The reaction mixture was stirred for 30 minutes at 70° C. and evaporated in presence of Isolute® sorbent to dryness. The crude product was purified by flash chromatography with a 20 g silica gel column eluting with heptane:ethyl acetate 100:0→70:30. The desired 5-(3-fluoro-phenylethynyl)-pyridine-2-carboxylic acid tert-butyl-methyl-amide (64 mg, 99% yield) was obtained as a colorless oil, MS: m/e=311.5 (M+H+).

Workup

  1. customevaporated in presence of Isolute® sorbent to dryness
  2. customThe crude product was purified by flash chromatography with a 20 g silica gel column
  3. washeluting with heptane:ethyl acetate 100:0→70:30

Sources & evidence

ORD record
ord-cebd0a3063dc4ad98d9a0797b2cfbedf
Source dataset
uspto-grants-2014_07
Patent number
US08772300B2

Reaction notes

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