- Development of [3]ferrocenophane-derived N/B frustrated Lewis pairs for the metal-free catalytic hydrogenation of imines
-
A series of novel [3]ferrocenophane-derived N/B frustrated Lewis pairs (FLPs) were synthesized and successfully applied to the catalytic hydrogenation of imines in 71–93% yields. This approach could be easily conducted on gram scale and provided versatile synthetic route for the key intermediate of sertraline hydrochloride without heavy metal residues.
- Pan, Zhentao,Wang, Hui,Ling, Fei,Xiao, Lian,Song, Dingguo,Zhong, Weihui
-
p. 522 - 528
(2019/02/01)
-
- IMPROVED PROCESS FOR PREPARING AN INTERMEDIATE OF SERTRALINE
-
The present invention provides an improved process for preparation of N-[4-(3,4- dichlorophenyl)-3,4-dihydro-1-(2H)-naphthalenylidene]methanamine (ketimine) comprising condensation of 4-(3,4-dichlorophenyl)-3,4-dihydro-1-(2H)-naphthalenone (sertralone) with monomethyl amine gas in the presence of a dehydrating agent and an aprotic solvent.
- -
-
Page/Page column 7-8
(2010/08/08)
-
- PROCESS FOR THE PREPARATION OF AN IMINE INTERMEDIATE
-
The invention is directed to a process for the preparation of [4(S,R)-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalene-1-ylidene]-methyl-amine of the Formula (I) by reacting 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)naphthalene-l-one of the Formula (II) with monomethyl amine which comprises carrying out the reaction in the presence of thionyl chloride in an ether-type solvent. The [4(S,R)-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalene-1-ylidene]-methyl-amine of the Formula I is a valuable pharmaceutical intermediate.
- -
-
Page/Page column 11-12
(2008/06/13)
-
- A new and simplified process for preparing N-[4-(3,4-dichlorophenyl)-3,4- dihydro-1(2H)-naphthalenylidene]methanamine and a telescoped process for the synthesis of (1S-cis)-4-(3,4-dichlorophenol)-1,2,3,4-tetrahydro-N-methyl-1- naphthalenamine mandelate: Key intermediates in the synthesis of sertraline hydrochloride
-
N-[4-(3,4-Dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]-methanamine, sertraline imine (3), is an intermediate for the synthesis of Zoloft, sertraline hydrochloride (1). A cleaner, simpler, and more efficient alternative to the Schiff base-mediated formation of sertraline imine has been developed and is presented in this paper. The condensation reaction between 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalone, sertraline tetralone (2), and monomethylamine was carried out in ethanol, without the need for classical dehydrating agent, such as TiCl4, or more novel approaches, such as molecular sieves, both of which produce hazardous byproducts and solid wastes. The low solubility of the imine 3 in this type of solvent is exploited, such that the reaction equilibrium favorably enhances the imine formation. Furthermore, an improved and highly selective catalytic reduction of 3 with Pd/CaCO3 catalyst in ethanol as the reaction solvent, followed by the resolution of the racemic cis isomer (6) with D-(-)-mandelic acid results in a more efficient telescoped commercial process to (1S-cis)-4-(3,4-dichlorophenol)- 1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine mandelate, sertraline mandelate (4). This new process has been implemented commercially and eliminates the use of hazardous material such as TiCl4, significantly reduces undesirable byproducts, reduces the number of intermediate isolations, and improves the overall process yield and productivity on industrial scale.
- Taber, Geraldine P.,Pfisterer, David M.,Colberg, Juan C.
-
p. 385 - 388
(2013/09/05)
-
- METHOD OF PRODUCING KETIMINES
-
The invention relates to a method of producing compounds of formula (1), wherein R1, R2 and R3 are independently hydrogen, halogen, trifluoromethyl or C1-C4 alkoxy, characterized in that a compound of formula (2), wherein R1, R2 and R3 have the meanings defined in formula (1), is reacted with methyl amine in a protic solvent and (b) the obtained compound of formula (1) is purified by recrystallization and /or reaction step (a) is carried out in the presence of a catalyst.
- -
-
-
- Process for the preparation of ketimines
-
Described is a process for the preparation of compounds of formula (1a) which comprises reacting an isomeric mixture consisting of from 75 to 95% of compound of formula (2a) and from 5 to 25% of a compound of formula (2b) with methylamine, in a suitable solvent, to form a sertraline-imine isomeric mixture consisting of from 75 to 95% of formula (1a) and from 5 to 25% of formula (1b)(A1), or reacting an isomeric mixture consisting of from 75 to 95% of a compound of formula (2a) and from 5 to 25% of a compound of formula (2b) with methylamine, in a suitable solvent, using suitable methods of isolation to form an enriched sertraline-imine isomeric mixture, consisting of >99% of a compound of formula (1a) and 2); and then subjecting the sertraline-imine isomeric mixture obtained according to reaction route (A1) or (A2), in a suitable solvent, to recrystallisation (B), in accordance with scheme (I) wherein in formula (1a), R1, R2and R3are each independently of the others hydrogen, halogen, trifluoromethyl or C1-C4alkoxy and formulae (1b), (2a) and (2b) are as defined in the description.
- -
-
Page column 11-12
(2008/06/13)
-
- Process for the production of sertraline and intermediates useful therefor
-
A pharmaceutical intermediate, N-[4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]methanamine, which can be used in the production of sertraline hydrochloride, is conveniently prepared by reacting 4-(3,4-dichlorophenyl)-3,4-dihydro-1-(2H)-naphthalenone with monomethylamine in a solvent which is an amide solvent with a structure of general formula IV: wherein R1, R3 are independently hydrogen or C1-6 alkyl, which can be substituted, and R2 is hydrogen.
- -
-
-
- Process for preparing sertraline from chiral tetralone
-
This invention relates to a novel improved process for preparing the (+) enantiomer of N-[4(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]methanamine by reacting the (+) enantiomer of 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone with monomethylamine and titanium chloride or molecular sieves.
- -
-
-
- Nontricyclic Antidepressant Agents Derived from cis- and trans-1-Amino-4-aryltetralins
-
The need for drugs that lack the obtrusive and limiting side effects of the tricyclic antidepressants has prompted the search for agents with greatly enhanced selectivity for specific mechanisms believed to be essential for antidepressant efficacy.The potential role of derangements of 5-HT pathways in the etiology of depression has long been suspected and has given impetus to the development of newer compounds that accentuate inhibition of serotonin reuptake.This paper presents structure-activity relationship for a series of cis-1-amino-4-(substituted-aryl)tetralins, which are surprisingly potent and selective inhibitors of serotonin uptake in in vitro models.These compounds are pharmacologically distinct from corresponding members of the trans series, which also potently block uptake of dopamine and norepinephrine.The activity in both cis and trans series is stereospecific, being restricted to the cis-(1S,4S) and the trans-(1R,4S) enantiomers.
- Welch, Willard M.,Kraska, Allen R.,Sarges, Reinhard,Koe, B. Kenneth
-
p. 1508 - 1515
(2007/10/02)
-