Benzylethanolamine → 2-Carbamoyl-4-(2-methylphenyl)piperazine

Participants

Reaction Steps

2-Benzylaminoethanol (20 g, 0.13 mol) was converted to N-(2-chloroethyl)-N-benzylamine hydrochloride with thionyl chloride (31 g, 0.26 mol) according to the procedure described in J. Chem. Soc. 1955, p. 896. N-(2-chloroethyl)-N-benzylamine hydrochloride (4.0 g, 19 mmol) was converted to N-benzyl-N'-(2-methylphenyl)-1,2-diaminoethane hydrochloride by the procedure of Syn. Comm., 1988, vol. 18, p. 45-50, using o-toluidine (6.1 g, 57 mmol) in place of aniline. 1-Benzyl-2-carbamoyl-4-(2-methylphenyl)-piperazine was prepared from 2,3-dibromopropionamide (7.9 g, 34 mmol) by the procedure of J. Med. Chem., 1992, vol. 35, p. 743-750 using N-benzyl-N'-(2-methylphenyl)-1,2-diaminoethane hydrochloride (4.95 g, 18 mmol) in place of N-benzyl-N'-phenyl-1,2-diaminoethane hydrochloride (TLC: Rf=0.51 (5% methanol in methylene chloride; FABMS: M+H @ m/e=310). 1-Benzyl-2-carbamoyl-4-(2-methyl-phenyl)piperazine (2.64 g, 8.53 mmol) and palladium hydroxide/carbon (430 mg) were combined in a mixture of methanol (35 ml) and ethanol (35 ml) and shaken in an atmosphere of hydrogen at 55 psi for 6 hours at ambient temperature. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was reconcentrated in vacuo from ether three times to provide 2-carbamoyl-4-(2-methylphenyl)piperazine as a solid.

Provenance & Evidence