Triethylamine → 5-((4-Fluoro-3-formylphenyl)ethynyl)nicotinonitrile

HRID 606817Notes

Reaction equation

HRID 606817 reaction equation
C[Si]([C:5]#[C:6][C:7]1[CH:8]=[N:9][CH:10]=[C:11]([CH:14]=1)[C:12]#[N:13])(C)C.[F:15][C:16]1[CH:23]=[CH:22][C:21](I)=[CH:20][C:17]=1[CH:18]=[O:19].C(N(CC)CC)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[F:15][C:16]1[CH:23]=[CH:22][C:21]([C:5]#[C:6][C:7]2[CH:8]=[N:9][CH:10]=[C:11]([CH:14]=2)[C:12]#[N:13])=[CH:20][C:17]=1[CH:18]=[O:19]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 2724141Tetrabutylammonium FluorideHCID 161156995-[2-(Trimethylsilyl)ethynyl]pyridine-3-carbonitrileHCID 162170582-Fluoro-5-iodobenzaldehyde

Product 1

HCID 848197895-((4-Fluoro-3-formylphenyl)ethynyl)nicotinonitrileYield 45%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Combine 5-trimethylsilanylethynyl-nicotinonitrile (1.30 g, 11.5 mmol), (prepared as described in PREPARATION 3), 2-fluoro-5-iodobenzaldehyde (3.45 g, 13.8 mmol, (prepared essentially as described in Tet. Lett., 33, 7499, (1992)), bis(triphenylphosphine)palladium (II) dichloride (404 mg, 0.575 mmol), copper (I) iodide (219 mg, 1.15 mmol), and triethylamine (22.4 mL, 161 mmol) in tetrahydrofuran (9 mL). Cool the suspension to −78° C. and treat with a 1.0 M solution of tetrabutylammonium fluoride (11.5 mL) in tetrahydrofuran. After 10 min, heat to 60° C. for 2 h. Cool to room temperature and filter through diatomaceous earth washing with ethyl acetate. Purify the crude product by silica gel chromatography, eluting with a gradient from 80:20 to 60:40 hexanes:ethyl acetate, to give the title compound as an off-white crystalline solid (1.3 g, 45%).

Workup

  1. temperatureheat to 60° C. for 2 h
  2. temperatureCool to room temperature
  3. filtrationfilter through diatomaceous earth
  4. washwashing with ethyl acetate
  5. customPurify the crude product by silica gel chromatography
  6. washeluting with a gradient from 80:20 to 60:40 hexanes

Sources & evidence

ORD record
ord-1698521844fb41e3833d87586a72b2ff
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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