Process for the preparation of N-(2,3-dihydrobenzo 1,4 dioxin-2-carbonyl) piperazine

摘要

Preparation of N-(2,3-dihydrobenzo[1,4]dioxin-2-carbonyl)piperazine involves heating a reaction mixture of ethyl 2,3-dihydrobenzo[1,4]dioxin-2-carboxylate and piperazine in a molar ratio of 1:2-2:1 under nitrogen atmosphere at 70-90 [deg]C for 3-15 hours, cooling the mixture to 25-30 [deg]C and performing acid base work-up procedure to obtain (I) in amorphous solid form. Preparation of N-(2,3-dihydrobenzo[1,4]dioxin-2-carbonyl piperazine (I) involves: (1) heating a reaction mixture of ethyl 2,3-dihydrobenzo[1,4]dioxin-2-carboxylate and piperazine in a molar ratio of 1:2-2:1 under nitrogen atmosphere at 70-90 (preferably 75-80)[deg]C for 3-15 (preferably 5-12) hours; (2) cooling the mixture to 25-30 [deg]C and dissolving in chloroform (a) followed by washing with saturated sodium bi-carbonate solution and water respectively; (3) acidifying the organic layer by 10% HCl to a pH of 1-4, separating the organic layer and washing the aqueous layer with (a); and (4) basifying the aqueous layer with sodium bi-carbonate to pH of 7-9 followed by extracting with (a) and evaporating the chloroform to obtain (I) in amorphous solid form.