Trimethylsilylacetylene → 2-(4-ethynyl-2-fluoroanilino)-3,4-difluoro-N-(2-hydroxyethoxy)-5-[(E)-(2-hydroxy-2-methylpropoxy)iminomethyl]benzamide

https://huagongshe.com/reaction/2038631

Participants

Role	Name	HCID	Charge
Reactant	Trimethylsilylacetylene	HCID 66111	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Tetrabutylammonium Fluoride	HCID 2724141	—
Reactant	Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)	HCID 6099338	—
Reactant	3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(E)-(2-hydroxy-2-methylpropoxy)iminomethyl]benzamide	HCID 11387506	—
Catalyst	Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)	HCID 24350	—
Solvent	Methanol	HCID 887	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	2-(4-ethynyl-2-fluoroanilino)-3,4-difluoro-N-(2-hydroxyethoxy)-5-[(E)-(2-hydroxy-2-methylpropoxy)iminomethyl]benzamide	HCID 11363286	574.9%

Reaction Steps

(E)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-hydroxy-2-methyl-propoxyimino)-methyl]-benzamide (200 mg, 0.35 mmol), Pd(CH3CN)2Cl2 (4.5 mg, 0.0176 mmol), triphenylphosphine-3,3′,3″-trisulfonic acid trisodium salt (25.0 mg, 0.037 mmol), N(iPr)2Et (48.0 mg, 0.37 mmol), trimethylsilyl acetylene (172 mg, 1.76 mmol), and CuI (3.4 mg, 0.0176 mmol) were stirred in MeOH at room temperature for 1 hour, and the solvent was evaporated. The resultant residue was added to THF/H2O containing tetrabutylammonium fluoride (0.35 mmol), and the mixture was stirred for 1 hour. EtOAc was added thereto, and the organic layer was washed with 0.4 N aqueous HCl, dried over Na2SO4, and evaporated. The resultant residue was purified by silica gel chromatography (CH2Cl2/MeOH as a developing solvent) to give a title compound (99 mg).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08575391B2
Source dataset	uspto-grants-2013_11
ORD ID	ord-a8fb2c19e02c4eab928a827c56d1bc04
Source note	uspto-grants-2013_11