Triflusal → Acetic acid 2-chlorocarbonyl-5-trifluoromethylphenyl ester

To a stirred solution of 2-acetoxy-4-trifluoromethyl-benzoic acid (180 mg, 0.73 mmol) in CH2Cl2 (6 mL) were added oxalyl chloride (0.08 mL, 0.91 mmol) and DMF (1 drop). The reaction mixture was stirred at room temperature for 1 hour. CH2Cl2 and excess oxalyl chloride were removed in vacuo. Acetic acid 2-chlorocarbonyl-5-trifluoromethylphenyl ester was obtained as a colorless oil (190 mg) and used in the following step without further purification. To a stirred solution of [1-Methyl-6-(5-methylaminopyridin-2-yloxy)-1H-indol-2-yl]{4-[4-(2,2,2-tri-fluoroethoxy)benzyl]piperazin-1-yl}methanone (340 mg, 0.6 mmol) in AcOEt (4 mL) were added triethylamine (0.13 mL, 0.91 mmol) and acetic acid 2-chlorocarbonyl-5-trifluoromethyl-phenyl ester (190 mg, 0.73 mmol) in AcOEt (3 mL) under ice cooling. The reaction mixture was stirred for 10 minutes at 0° C. Water was added to the reaction mixture, and the aqueous layer was extracted with AcOEt. The organic layer was washed with saturated aqueous NaHCO3 and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (CH2Cl2:MeOH=50:1) to afford 0.46 g of the title compound as a white powder.

1. customCH2Cl2 and excess oxalyl chloride were removed in vacuo

ORD record

ord-0c3215dbfe1c4a0191bd04296f1eac82

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08551999B2