Diisopropylethylamine → 5-(5-Cyanopyridin-3-ylethynyl)-2-fluorobenzoic acid methyl ester

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Tris(1,1-dimethylethyl)phosphine	HCID 83681	—
Reactant	Methyl 5-bromo-2-fluorobenzoate	HCID 21525435	—
Reactant	5-Ethynylnicotinonitrile	HCID 22416563	—
Catalyst	Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)	HCID 24350	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	5-(5-Cyanopyridin-3-ylethynyl)-2-fluorobenzoic acid methyl ester	HCID 67047625	44.1%

Reaction Steps

Sequentially add tri-tert-butylphosphine (88 mg, 0.437 mmol) in anhydrous 1,4-dioxane (1 mL), diisopropylethylamine (1.5 mL, 8.74 mmol), 5-bromo-2-fluorobenzoic acid methyl ester, (prepared as described in PREPARATION 42), (1.69 g, 7.28 mmol) and a solution of 5-ethynylnicotinonitrile, (prepared as described in PREPARATION 4), (0.93 g, 7.28 mmol) in anhydrous 1,4-dioxane (4 mL), to a stirring mixture of dichloro(benzonitrile)palladium (II) (84 mg, 0.218 mmol) and copper (I) iodide (28 mg, 0.146 mmol) in anhydrous 1,4-dioxane (1 mL) under nitrogen. Stir for 2 h and concentrate. Purify the residue twice by silica gel chromatography, eluting with 10:90 ethyl acetate:hexanes, to give the title compound as a white solid (0.9 g, 44%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07915424B2
Source dataset	uspto-grants-2011_03
ORD ID	ord-43d1c1dd35034439a698b92cd8d3b32f
Source note	uspto-grants-2011_03