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Crystalline form of 1-(benzo[b]thiophen-4-yl)piperazine dihydrochloride salt

IP.com Disclosure Number: IPCOM000249236D
Publication Date: 2017-Feb-12
Document File: 2 page(s) / 374K

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 58% of the total text.

Crystalline form of 1-(benzo[b]thiophen-4-yl)piperazine dihydrochloride salt

1-(benzo[b]thiophen-4-yl)piperazine dihydrochloride (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 gives Compound III.

These two steps are summarized in the following scheme:

Preparation of tert-butyl 4-(benzo[b]thiophen-4-yl) piperazine-1-carboxylate [Compound II]

A 100L reactor loaded with 10% Pd/C (50% wet, 150 g) and toluene (30 L). The water

was removed by azeotropic distillation upon heating (Tj~123 °C). Then, the mixture was

cooled to 25 o C followed by addition of 4-bromobenzo[b]thiophene (Compound I, 3 Kg,

14 mol), racemic BINAP (66 gr, 0.1 mol) and NatOBu (2.7 Kg, 28 mol). The reaction

mixture was heated to 100 °C and stirred at this temperature for 3 hours until full

consumption of Compound I was obtained (LT-0.5% by HPLC). Then, the reaction

mixture was cooled to 40 °C. A solution of 5% citric acid (30 L) was added and the

reaction mixture was stirred at 40 °C for about 20 minutes. The mixture was filtrated by

cartridge filter and washed with water (30 L). The filtrate was loaded in the reactor and

heated to...