Ammonium Chloride → 6-(2-Amino-pyrimidin-4-yloxy)-benzofuran-3-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

Participants

Reaction Conditions

Reaction Steps

In a dried vessel, 108 mg (0.60 mMol) 4-fluoro-3-trifluoromethyl-aniline are dissolved in 10 ml toluene and cooled to 10° C. Then 900 μl Me3Al (2 M in toluene; 1.8 mMol) are added via syringe. After 1 h at rt, a suspension of 171 mg (0.599 mMol) 6-(2-amino-pyrimidin-4-yloxy)-benzofuran-3-carboxylic acid methyl ester (Step 9.6) in 5 ml THF is added and the reaction mixture is stirred for 40 min in an oil bath of 110° C. The solution is cooled in ice and hydrolyzed with 20 ml of a sat. NH4Cl. After 10 min stirring, the mixture is filtered through Celite, the solid washed extensively with EtOAc and water, the aq. phase separated from the filtrate and extracted with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Column chromatography (SiO2; EtOAc) and crystallization from EtOAc/hexane 1:1 gives the title compound: MS: [M+1]+=433; TLC(hexane/EtOAc 1:9): Rf=0.22.

Provenance & Evidence