Oxalyl chloride → Tert-butyl 2-(2-hydroxy-4-(trifluoromethyl)benzamido)ethylcarbamate

Participants

Reaction Steps

To a solution of 2-hydroxy-4-(trifluoromethyl)benzoic acid (0.5 g, 2.4 mmol) in CH2Cl2 (8 mL) was added oxalyl chloride (0.46 g, 3.6 mmol) and 2 drops of DMF. The reaction was stirred (RT, 2 h) and then concentrated under reduced pressure. The resulting residue was dissolved in CH2Cl2 (8 mL) and tert-butyl 2-aminoethylcarbamate (0.39 g, 2.4 mmol) and diisopropylethylamine (0.41 g, 3.2 mmol) were added. The reaction was stirred (RT, 16 h) and then partitioned between CH2Cl2 and brine. The aqueous layer was extracted with CH2Cl2 and the combined organic extracts were dried over MgSO4. The crude material was purified by silica gel chromatography (0-10% MeOH/CH2Cl2) to afford tert-butyl 2-(2-hydroxy-4-(trifluoromethyl)benzamido)ethylcarbamate (0.55 g). Mass calculated for C15H19F3N2O4=348.32; found: [M+Na]+=371.1. This was then dissolved in CH2Cl2 (10 mL) and TFA (4 mL). The reaction was stirred (RT, 3 h) and concentrated and dried to afford N-(2-aminoethyl)-2-hydroxy-4-(trifluoromethyl)benzamide (0.7 g) as a clear oil. Mass calculated for C10H11F3N2O2=248.20; found: [M+H]+=249.1.

Provenance & Evidence