Diisopropylethylamine → 4-Benzyl-1-(4-fluoro-2-methyl-phenyl)-piperazine-2-carboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To N-benzyl-N′-(4-fluoro-2-methyl-phenyl)-ethane-1,2-diamine (15.1 g) in toluene (150 mL) was added N,N-diisopropylethylamine (33.8 mL) and 2,3-dibromopropionic acid ethyl ester (25.61 mL) in toluene (350 mL). The reaction mixture was heated to 135° C. for 18 h, cooled to room temperature, and the precipitated solid was removed by filtration. The solution was concentrated, and the crude material was redissolved in TBME and washed with an aqueous 2M solution of Na2CO3 and brine, dried (Na2SO4), filtered and evaporated. Chromatography (SiO2, n-heptane/ethyl acetate 97:3) gave 4-benzyl-1-(4-fluoro-2-methyl-phenyl)-piperazine-2-carboxylic acid ethyl ester (5.5 g) as yellow oil, MS: 357.3 ([M+H]+) and 1-benzyl-4-(4-fluoro-2-methyl-phenyl)-piperazine-2-carboxylic acid ethyl ester (3.3 g) as yellow oil, MS: 357.1 ([M+H]+).

Provenance & Evidence