公开(公告)号：US20220204455A1

公开(公告)日：2022-06-30

申请号：US17617598

申请日：2020-06-19

Applicant: Procos S.P.A.

Inventor： Monica Donnola ,  Alessandro Barozza ,  Jacopo Roletto ,  Paolo Paissoni

IPC: C07D233/22

Abstract: Disclosed is a process for the synthesis of lofexidine of formula (I) and the hydrochloride salt thereof (II), from ethyl 2-(2,6-dichlorophenoxy)propionate (III) and ethylenediamine in the presence of tetravalent titanium alkoxides, preferably titanium isopropoxide, in an apolar solvent such as toluene. A further object of the present invention is a process for the preparation of the intermediate ethyl 2-(2,6-dichlorophenoxy)propionate (III) from 2,6-dichlorophenol and ethyl 2-chloropropionate in the presence of a polar aprotic solvent and an alkali or alkaline earth carbonate salt, preferably potassium carbonate. Both processes are more cost-effective and more easily industrially scalable than the known procedures, thus enabling the active ingredient to be obtained with high yields at a limited cost.

公开(公告)号：US09567308B1

公开(公告)日：2017-02-14

申请号：US15214499

申请日：2016-07-20

Applicant: Procos S.P.A.

Inventor： Luigi Bogogna ,  Lavinia Cicione ,  Alessandro Barozza ,  Jacopo Roletto ,  Paolo Paissoni

IPC: C07D263/58

CPC classification number: C07D263/58

Abstract: Disclosed is a process for the synthesis of chlorzoxazone (1) from 4-chloro-2-aminophenol and ethyl chloroformate in the presence of a base. The process is particularly advantageous because it uses ethyl chloroformate instead of triphosgene, a highly dangerous reagent that releases phosgene and must be handled with extremely strict procedures to guarantee the safety of operators in industrial facilities.Ethyl chloroformate allows the possibility of working with a number of solvents, including water.The yield and purity of the product obtained are very high.

Abstract translation: 获得的产物的产率和纯度非常高。

公开(公告)号：US10472325B2

公开(公告)日：2019-11-12

申请号：US15771050

申请日：2016-10-27

Applicant: PROCOS S.p.A.

Inventor： Matteo Mossotti ,  Alessandro Barozza ,  Jacopo Roletto ,  Paolo Paissoni

IPC: C07D213/64

Abstract: Disclosed is a process for the synthesis of Pirfenidone (1) from 5-methyl-2(1H)-pyridinone and chlorobenzene in the presence of a catalytic system consisting of a copper salt and an organic ligand, in the presence of a base. The process exploits the high efficiency of the catalytic system consisting of copper(I) salt and an organic ligand in the presence of an inorganic base in the N-amidation reaction of chlorobenzene, a cheap reagent also usable as solvent in this case; reaction conditions at high temperatures, at atmosphere pressure or higher, produce a reaction with good yields.

公开(公告)号：US11459303B2

公开(公告)日：2022-10-04

申请号：US17617598

申请日：2020-06-19

Applicant: Procos S.P.A.

Inventor： Monica Donnola ,  Alessandro Barozza ,  Jacopo Roletto ,  Paolo Paissoni

IPC: C07D233/22

Abstract: Disclosed is a process for the synthesis of lofexidine of formula (I) and the hydrochloride salt thereof (II), from ethyl 2-(2,6-dichlorophenoxy)propionate (III) and ethylenediamine in the presence of tetravalent titanium alkoxides, preferably titanium isopropoxide, in an apolar solvent such as toluene. A further object of the present invention is a process for the preparation of the intermediate ethyl 2-(2,6-dichlorophenoxy)propionate (III) from 2,6-dichlorophenol and ethyl 2-chloropropionate in the presence of a polar aprotic solvent and an alkali or alkaline earth carbonate salt, preferably potassium carbonate. Both processes are more cost-effective and more easily industrially scalable than the known procedures, thus enabling the active ingredient to be obtained with high yields at a limited cost.

公开(公告)号：US20170022172A1

公开(公告)日：2017-01-26

申请号：US15214499

申请日：2016-07-20

Applicant: Procos S.P.A.

Inventor： Luigi Bogogna ,  Lavinia Cicione ,  Alessandro Barozza ,  Jacopo Roletto ,  Paolo Paissoni

IPC: C07D263/58

CPC classification number: C07D263/58

Abstract: Disclosed is a process for the synthesis of chlorzoxazone (1) from 4-chloro-2-aminophenol and ethyl chloroformate in the presence of a base. The process is particularly advantageous because it uses ethyl chloroformate instead of triphosgene, a highly dangerous reagent that releases phosgene and must be handled with extremely strict procedures to guarantee the safety of operators in industrial facilities.Ethyl chloroformate allows the possibility of working with a number of solvents, including water.The yield and purity of the product obtained are very high.

Abstract translation: 获得的产物的产率和纯度非常高。