EP1401800A1 - Neues verfahren zur herstellung von (1s cis) 4 (3,4 dichlorphenyl) 1,2,3,4-tetrahydro-n-methyl-1-naphthalinamin - Google Patents

Neues verfahren zur herstellung von (1s cis) 4 (3,4 dichlorphenyl) 1,2,3,4-tetrahydro-n-methyl-1-naphthalinamin

Info

Publication number
EP1401800A1
EP1401800A1 EP02743288A EP02743288A EP1401800A1 EP 1401800 A1 EP1401800 A1 EP 1401800A1 EP 02743288 A EP02743288 A EP 02743288A EP 02743288 A EP02743288 A EP 02743288A EP 1401800 A1 EP1401800 A1 EP 1401800A1
Authority
EP
European Patent Office
Prior art keywords
cis
dichlorophenyl
tetrahydro
naphthalenamine
methyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP02743288A
Other languages
English (en)
French (fr)
Inventor
Ilpo Laitinen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Orion Oyj
Original Assignee
Orion Yhtyma Fermion Oy
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from FI20011271A external-priority patent/FI20011271A0/fi
Application filed by Orion Yhtyma Fermion Oy filed Critical Orion Yhtyma Fermion Oy
Publication of EP1401800A1 publication Critical patent/EP1401800A1/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
    • C07C209/70—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by reduction of unsaturated amines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/82—Purification; Separation; Stabilisation; Use of additives
    • C07C209/86—Separation
    • C07C209/88—Separation of optical isomers

Definitions

  • the present invention relates to a novel process for the preparation of (1S- cis)-4-(3 ,4-dichlorophenyl)- 1 ,2,3 ,4-tetrahydro-N-methyl- 1 -naphthalenamine (sertraline) comprising hydrogenation of N-[4-(3,4-dichlorophenyl)-3,4-dihydro- 5 1 (2H)-naphthalenylidene]methanamine.
  • One object of the present invention is to provide an improved preparation method for cis-sertraline or a pharmaceutically acceptable acid addition salt thereof.
  • the other object of the present invention is the pharmaceutical composition comprising cis-sertraline or a pharmaceutically acceptable acid addition salt thereof made by the process of the invention.
  • the present invention provides a process for the preparation of cis-sertraline comprising hydrogenating N-[4-(3,4-dichlorophenyl)-3,4-dihydro-l(2H)- naphthalenylidene]methanamine in the presence of a catalyst and a dehalogenation inhibitor to achieve cis-racemate of 4-(3,4-dichlorophenyl)-l,2,3,4-tetrahydro-N- methyl- 1 -naphthalenamine.
  • the ratio of cis:trans isomers is improved to as high as 97:3 and the formation of dehalogenation byproducts may be reduced to even less than 0.1 %. No further purification process is needed before resolution or crystallization. This is achieved by using the inhibitors of the invention in the hydrogenation process.
  • Cis-sertraline is prepared starting from 4-(3 ,4-dichlorophenyl)-3 ,4-dihy dro- 1 -
  • (2H)-naphthalenone (tetralone), which can be prepared by methods known in the art, e.g. as decsribed in US 5,019,655. Tetralone is reacted with monomethylamine to form an imine, which can be performed by methods known in the art, e.g. as described in US 4,536,518.
  • the imine obtained is further hydrogenated to cis- racemate of 4-(3 ,4-dichlorophenyl)- 1 ,2,3 ,4-tetrahydro-N-methyl- 1 -naphthalenamine in the presence of a catalyst and a dehalogenation inhibitor of the invention. From this mixture, the cis-compound can be either resolved by e.g.
  • the hydrogenation of the imine is performed in the presence of a catalyst and an inhibitor, which is selected from the group consisting of hypophosphorous acid, esters of hypophosphorous acid, phosphorous acid, esters of phosphorous acid, phosphine and substituted phosphines.
  • Suitable inhibitors are e.g. mono-,di- and triesters of phosphorous acid, preferably trimethyl phosphite, triphenyl phosphite or tritolyl phosphite.
  • suitable phosphines are e.g. trimethylphosphine, triethylphosphine, triisopropylphosphine, tritolylphosphine and tribenzylphosphine.
  • the amount of the inhibitor used in the process is typically 0.5 - 10 mol %, preferably 3 - 5 mol %, based on the number of moles of the metal in the catalyst used.
  • the catalyst used can be any suitable catalyst known in the art, e.g. palladium on carbon, palladium on graphite, palladium on carbon paste or PtO 2 .
  • the catalyst is typically used in the amount of 0.1 - 1.0 % (w/w, calculated as the pure metal in the catalyst) based on the weight of the imine used.
  • the hydrogenation may be carried out in an organic solvent, which can be any suitable protic or aprotic solvent or mixtures thereof. Examples of solvents are e.g.
  • dimethylformamide DMF
  • esters like ethyl acetate, chlorinated hydrocarbons like methylene chloride or chloroform, or alcohols like methanol, ethanol or isopropanol.
  • alcohols like methanol, ethanol or isopropanol.
  • a lower alcohol e.g. methanol or ethanol or their mixture with DMF is used as a solvent.
  • the reaction can be carried out at a temperature of 0-100 °C, preferably at 20 - 50 °C.
  • the hydrogen pressure used is from 1 to 50 bar, preferably from 2 to 5 bar.
  • the reaction time can vary from half an hour to 24 hours depending on the catalyst used, on hydrogen pressure, on the reaction temperature and on the equipment used.
  • the hydrogenation time is about 2 to 6 hours.
  • N-[4-(3,4-dichlorophenyl)-3,4-dihydro-l-(2H)-naphthalenylidene]-methanamine 50 g
  • methanol 300 ml
  • palladium on graphite 5 % 2.5 g
  • trimethyl phosphite 0.004 g
  • the reaction mixture is hydrogenated at 5 bar overpressure of hydrogen for 5 hours at about 40 °C.
  • the catalyst is removed by filtration and the cake is washed with methanol.
  • the cis:trans ratio is 97:3.
  • the amount of dehalogenation byproducts is ⁇ 0.1 %.
  • the reaction mixture can be used directly in the resolution step or crystallized as HC1 salt.
  • N-[4-(3,4-Dichlorophenyl)-3,4-dihydro-l(2H)-naphthalenylidene]methanamine 40 g
  • dimethylformamide 150 ml
  • methanol 150 ml
  • palladium on graphite catalyst 4 g
  • triphenyl phosphite 0.0010 g

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
EP02743288A 2001-06-15 2002-06-14 Neues verfahren zur herstellung von (1s cis) 4 (3,4 dichlorphenyl) 1,2,3,4-tetrahydro-n-methyl-1-naphthalinamin Withdrawn EP1401800A1 (de)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US29808801P 2001-06-15 2001-06-15
FI20011271 2001-06-15
FI20011271A FI20011271A0 (fi) 2001-06-15 2001-06-15 Valmistusmenetelmä
US298088P 2001-06-15
PCT/FI2002/000518 WO2002102761A1 (en) 2001-06-15 2002-06-14 A novel process for the preparation of (is-cis) -4-(3, 4-dichlorophenyl) -1, 2, 3, 4 - tetrahydro-n-methyl-1-naphthalenamine

Publications (1)

Publication Number Publication Date
EP1401800A1 true EP1401800A1 (de) 2004-03-31

Family

ID=26161186

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02743288A Withdrawn EP1401800A1 (de) 2001-06-15 2002-06-14 Neues verfahren zur herstellung von (1s cis) 4 (3,4 dichlorphenyl) 1,2,3,4-tetrahydro-n-methyl-1-naphthalinamin

Country Status (3)

Country Link
EP (1) EP1401800A1 (de)
CA (1) CA2448499A1 (de)
WO (1) WO2002102761A1 (de)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2522534A1 (en) * 2003-04-14 2004-10-28 Teva Pharmaceutical Industries Ltd. Hydrogenation of imine intermediates of sertraline with catalysts
WO2005121074A2 (en) * 2004-06-09 2005-12-22 Ranbaxy Laboratories Limited Processes for the preparation of sertraline hydrochloride
GB0526444D0 (en) * 2005-12-23 2006-02-08 Sandoz Ag Sertraline acid addition salt, its prepartion and its use in the preparation of sertraline hydrochloride form ll
TR200808115T1 (tr) * 2006-04-28 2009-03-23 Sandoz Ag 4(S,R)-(3,4-diklorofenil)-3,4-dihidro-l(2H)-naftalin-l-ilid n]metilamin'ın Hazırlanması için Proses.@
CN111632400B (zh) * 2020-06-21 2022-04-05 赤峰制药股份有限公司 一种烯胺盐重结晶纯化方法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3474144A (en) * 1966-08-17 1969-10-21 Gaf Corp Catalytic reduction of chloronitro aromatic compounds
US4020107A (en) * 1975-04-07 1977-04-26 E. I. Du Pont De Nemours And Co. Catalytic reduction of halonitroaromatic compounds
US4536518A (en) * 1979-11-01 1985-08-20 Pfizer Inc. Antidepressant derivatives of cis-4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine
IT1205040B (it) * 1987-05-28 1989-03-10 Rimar Chimica Spa Processo per la riduzione catalitica di nitroalogenoderivati aromatici
HU226424B1 (en) * 1998-05-05 2008-12-29 Egis Gyogyszergyar Nyrt Process for producing enantiomer mixture for preparation of sertraline
JP2003527359A (ja) * 2000-03-14 2003-09-16 テバ ファーマシューティカル インダストリーズ リミティド （＋）−シス−セルトラリンの製造のための新規方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO02102761A1 *

Also Published As

Publication number Publication date
WO2002102761A1 (en) 2002-12-27
CA2448499A1 (en) 2002-12-27

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