4-(1,4-diazepan-1-ylmethyl)benzonitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of homopiperazine (9.2 g, 92 mmol, 2 equiv). in EtOH (115 mL) was added 1 M HCl-EtOH (92 mL) dropwise over 1 h. The suspension was heated to 70° C. for 1 h at which point a homogeneous solution of monohydrochloride salt was obtained. α-Bromo-p-tolunitrile (9.0 g, 46 mnmol, 1 equiv) was added and the reaction mixture was heated to reflux for 5 h. After cooling, the solvent was removed by rotary evaporation and the residue was partitioned between CH2Cl2 (100 mL) and 2N aqueous KOH (100 mL). The aqueous layer was extracted with CH2Cl2 (5×50 mL) and the combined organic phase was washed with saturated aqueous NaCl (1×150 mL) and dried (MgSO4). Chromatography (SiO2, 4×20 cm, 20% CH3OH —5% Et3N—CH2Cl2) afforded the desired monoalkylated material (6.78 g, 10.1 g theoretical, 67%) as an amber oil. was obtained the reaction mixture was heated to reflux for 5 h After cooling the solvent was removed by rotary evaporation the residue was partitioned between CH2Cl2 (100 mL) and 2N aqueous KOH (100 mL) The aqueous layer was extracted with CH2Cl2 (5×50 mL) the combined organic phase was washed with saturated aqueous NaCl (1×150 mL) dried (MgSO4) Chromatography (SiO2, 4×20 cm, 20% CH3OH —5% Et3N—CH2Cl2) afforded the desired monoalkylated material (6.78 g, 10.1 g theoretical, 67%) as an amber oil