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

Participants

Role	Name	HCID	Charge
Reactant	Tetrabutylammonium Fluoride	HCID 2724141	—
Reactant	2-Chloro-1-fluoro-4-iodobenzene	HCID 2724605	—
Reactant	5-[2-(Trimethylsilyl)ethynyl]pyridine-3-carbonitrile	HCID 16115699	—
Catalyst	Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)	HCID 24350	—
Catalyst	HCID 178419050	HCID 178419050	—
Solvent	Tetrahydrofuran	HCID 8028	—
Solvent	Triethylamine	HCID 8471	—
Product	5-(3-Chloro-4-fluorophenylethynyl)-nicotinonitrile	HCID 67047873	31.2%

Reaction Conditions

Temperature	-78 °C

Reaction Steps

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%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07915424B2
Source dataset	uspto-grants-2011_03
ORD ID	ord-4f3b00edf9ae4ed39fef8d6ae97bec4e
Source note	uspto-grants-2011_03