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Synthesis of 1-(benzo[b]thiophen-4-yl)piperazine hydrochloride salt

IP.com Disclosure Number: IPCOM000245732D
Publication Date: 2016-Apr-03
Document File: 2 page(s) / 482K

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The IP.com Prior Art Database

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Synthesis of 1-(benzo[b]thiophen-4-yl)piperazine hydrochloride salt

1-(benzo[b]thiophen-4-yl)piperazine hydrochloride salt (referred to as Compound III) has the following structure:

Compound III is obtained by a process as shown in the scheme below:

The synthesis of compound III involves a reaction between 4- bromobenzo[b]thiophene (referred to as Compound I) and tert-butyl piperazine-1-carboxylate to give tert-butyl 4-(benzo[b]thiophen-4-yl) piperazine-1-carboxylate (referred to as Compound II). Next, removal of the Boc moiety upon acidic conditions give 1-(benzo[b]thiophen-4-yl)piperazine hydrochloride salt (referred to as Compound III).

These two steps are summarized in the following scheme:

Preparation of 1-(benzo[b]thiophen-4-yl)piperazine hydrochloride salt

Azaotropic distillation for a mixture of 10% Pd/C (50% wet, 0.753 gr, 15% w/w) in Toluene (135 ml), followed by addition of 4-bromobenzo[b]thiophene (Compound I, 5 gr), BINAP (0.220 gr), tert-butyl piperazine-1-carboxylate


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(5.27 g) and NatOBu (3.28 g). The reaction mixture was stirred at reflux till complete consumption of 4-bromobenzo[b]thiophene (Compound I) was obtained.

Water was added to the reaction mixture at room temperature followed by filtration through hyflow and washing with toluene. Next, 23% w/w HCl/EtOH was added to the separated toluene phase while stirring at room temperature. The obtained precipitation was collected by filtration, washed with EtOH and dried to give the cor...