Tetrabutylammonium Fluoride → 5-(3-Chloro-4-fluorophenylethynyl)-nicotinonitrile

HRID 606860Notes

Reaction equation

HRID 606860 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.[Cl:15][C:16]1[CH:21]=[C:20](I)[CH:19]=[CH:18][C:17]=1[F:23].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(N(CC)CC)C.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>[Cl:15][C:16]1[CH:21]=[C:20]([C:5]#[C:6][C:7]2[CH:8]=[N:9][CH:10]=[C:11]([CH:14]=2)[C:12]#[N:13])[CH:19]=[CH:18][C:17]=1[F:23]

Participants

8

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 27246052-Chloro-1-fluoro-4-iodobenzeneHCID 161156995-[2-(Trimethylsilyl)ethynyl]pyridine-3-carbonitrile

Product 1

HCID 670478735-(3-Chloro-4-fluorophenylethynyl)-nicotinonitrileYield 31.2%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-78 °C

Procedure

Stir 5-trimethylsilanylethynyl-nicotinonitrile (300 mg, 1.5 mmol), (prepared essentially as described in PREPARATION 3), 2-chloro-1-fluoro-4-iodobenzene (390 mg, 1.5 mmol), bis(triphenylphosphine)palladium (II) dichloride (50 mg, 0.08 mmol) and copper (I) iodide (20 mg, 0.15 mmol) in triethylamine (15 mL) under nitrogen and cool to −78° C. Add a 1 M solution of tetrabutylammonium fluoride (1.5 mL) in tetrahydrofuran and warm to room temperature and then heat at 70° C. until complete by thin layer chromatography. Concentrate and purify the residue by silica gel chromatography, eluting with hexanes:ethyl acetate, and then recrystallize from hexanes:ethyl acetate to give the title compound (120 mg, 31%).

Workup

  1. custom(prepared essentially
  2. temperaturewarm to room temperature
  3. temperatureheat at 70° C. until complete by thin layer chromatography
  4. concentrationConcentrate
  5. custompurify the residue by silica gel chromatography
  6. washeluting with hexanes
  7. customethyl acetate, and then recrystallize from hexanes

Sources & evidence

ORD record
ord-4f3b00edf9ae4ed39fef8d6ae97bec4e
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

Loading…