Chemoselective N-deprotection of tert-butyl 2-(trifluoroacetylamino) esters under PTC conditions: synthesis of tert-butyl 2-aminocarboxylates

Abstract

Trifluoroacetamide 1 is alkylated in good yields (77–83%) by tert-butyl 2-bromocarboxylates 3 under solid-liquid phase transfer catalysis (PTC) conditions [anhydrous K₂CO₃, triethyl(benzyl)ammonium chloride (TEBA; 10%), MeCN, 80 °C]. The resulting tert-butyl 2-(trifluoroacetylamino) carboxylates 5 are chemoselectively hydrolysed in 75–95% yields to the corresponding tert-butyl 2-amino carboxylates, isolated as hydrochlorides 8, under liquid-liquid PTC conditions [CH₂Cl₂ or Et₂O, aqueous 20% KOH, TEBA (10%), 25–40 °C].