PIPERAZINE-2-CARBOXYLIC ACID synthesis

Yield:54969-33-4 84.8%

Reaction Conditions:

with triethylamineHeating / reflux;

Steps:

1-4.1

To the preheated solution (50 C) of 2,3-dibromo-propionic acid methyl ester in toluene (40 ml) and Et3N (5.80 ml, 41.6 mmol), was added N, N -DIBENZYL-ETHANE-1, 2-diamine (4.90 ml, 20.8 mmol) dropwise. Resulting white slurry was heated to reflux to a clear solution and the solution was stirred at reflux overnight. After cooled to room tempera- ture, the reaction mixture was extracted with 2N HCl (ca. 500 ml) and the extract was neutralized with 4N NaOH. The aqueous layer was extracted with EtOAc three times. The organic layer was washed with brine, dried over MGS04, and concentrated to give 1,4- dibenzyl-piperazine-2-carboxylic acid methyl ester (5.73 g, 84.8%) as a colorless oil: HPLC-MS (ESI): Calcd for C2OH24N202 [M+H] + 325, found: 325.

References:

WO2004/84898,2004,A1 Location in patent:Page/Page column 46-47