- AN IMPROVED PROCESS FOR MINIMISING THE FORMATION OF DEHALOGENATED BYPRODUCTS
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The present invention provides an improved process for preparation of organic compounds represented by Formula-Z; wherein effectively minimising the formation of dehalogenated by-products is achieved. In the process, the reduction is carried out using suitable reducing agent; more preferably Lithium Aluminium Hydride (LAH) in a solvent system, wherein at least one of the solvent is selected from halogenated solvents, which acts as co-solvent. The process of the present invention is useful for minimising of the formation of dehalogenated by-products during synthesis of various active pharmaceutical ingredients such as Paroxetine Hydrochloride, Cinacalcet, Eletriptan and Asenapine.
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Page/Page column 17
(2015/06/03)
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- PREPARATION OF PAROXETINE HYDROCHLORIDE HEMIHYDRATE
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A process for preparing paroxetine hydrochloride hemihydrate.
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Page/Page column 8
(2008/06/13)
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- Process for preparing (+)trans-4-p-fluorophenyl-3-hydroxymethyl-1-methylpiperidine
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The present invention relates to a process for preparing (±)-trans-4-p-fluorophenyl-3-hyroxymethyl-1-methylpiperdine of formula (I). The present invention also relates to novel intermediates of the formula (IX) and (IX′) methods for preparing said intermediates and the use of said compounds for preparing Paroxetine and Omiloxetine.
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- Novel process
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A process for the manufacture of the (?) trans piperidine carbinol (1) by a process comprising contacting a racemic mixture of the piperidine carbinol in solution with (?)-ditoluoyltartaric acid, crystallising the (?) -ditoluoyltartaric acid salt of the piperidine carbinol, isolating the crystalline salt and neutralising the crystalline salt to regenerate the (?) trans isomer of the piperidine carbinol and the (?)-ditoluoyltartaric acid, which is characterised by one or more of the following steps: (1) combining solutions of the racemic piperidine carbinol and (?)-ditoluoyltartaric acid in acetone so that the combined solution contains 2-3 % wt/wt of water, (2) consolidating the chiral salt crystallisation at from 30 to 40° C., (3) cooling the crystallisation mixture to from 3 to 7° C. before isolating the chiral salt, (4) regenerating the (?) trans piperidine carbinol at a pH of from 10.5 to 11.5, (5) forming a concentrated solution of the (?) trans piperidine carbinol in toluene, contacting the solution with heptane at 60-65 ° C., and cooling stepwise to crystallise the (?) trans piperidine carbinol. Alternatively, a solution of the racemic piperidine carbinol in toluene, suitably from a previous stage in the manufacture of paroxetine, is combined with a solution of (?)- ditoluoyltartaic acid in acetone. The resultant (?) trans piperidine carbinol of structure (1) may be coupled with sesamol, then deprotected, to give paroxetine (2), with optional formation of a pharmaceutically acceptable salt of paroxetine.
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- Novel process
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A process for the preparation of a 4-aryl-3-oxymethyl-piperidine of structure (1) in which R is hydrogen or an alkyl, arylalkyl, allyl, acyl, carbonyloxyalkyl, carbonyloxyaryl, or carbonyloxyalkylaryl group, and Y is a hydrogen atom or an optionally substituted alkyl, arylalkyl, or aryl group, from a carboxy derivative of structure (2) where A is oxygen or sulphar, X is one or more of hydrogen, or a readily reducible group, Z represents either a hydrogen atom or an OY′ group in which Y′ is independently selected from the same groups as Y, and the broken line circle indicates bonding, appropriate to a tetrahydropyridine, dihydropyridine, pyridine, or piperidine ring said process comprising (a) when Y is a hydrogen atom, reducing the compound of structure (2), or (b) when Y is other than a hydrogen atom (i) forming an ether from the alcohol product of step (a), (ii) etherifying the aldehyde compound of structure (2) in which Z is hydrogen, or (iii) reducing the ester compound of structure (2) in which Z is OY′.
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- Process for the preparation of 3-substituted 4-phenyl-piperidine derivative
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Described herein is the process for the preparation of 3-substituted 4-phenyl-piperidine derivatives of formula (I) in which X is selected from H and F, and R is selected from the group consisting of H, C1-C6 alkyl, C3-C6 alkenyl, and benzyl, comprising three steps starting from the monoamide of malonic acid and cinnamic aldehyde, or derivatives thereof.
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- Process for preparing arylpiperidine carbinol intermediates and derivatives
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A process for the synthesis of arylpiperidine carbinol intermediates and derivatives is disclosed. A preferred process embodiment provides the synthesis of intermediate compounds of structural formula (I) and structural formula (II): where X is halo, C1-C10 alkoxy, C1-C10 haloalkyl, or hydroxy; R2 and R3 are each C1-C4 alkyl, and R2 and R3 are the same. The compound of structural formula (I) is made by condensing a corresponding cinnamonitrile with a corresponding diester malonate. The compound of structural formula (II) in the (±)-trans configuration is obtained by hydrogenating the compound of structural formula (I). The compounds of structural formula (I) and structural formula (II) are useful chemical intermediates for synthesizing 4-arylpiperidine-3-carbinols and their derivatives in (?)-trans configuration.
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- Process for the preparation of 3-substituted 4-phenyl-piperidine derivatives
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Described herein is the process for the preparation of 3-substituted 4-phenyl-piperidine derivatives of formula (I) in which X is selected from H and F, and R is selected from the group consisting of H, C1-C6 alkyl, C3-C6 alkenyl, and benzyl, comprising three steps starting from the monoamide of malonic acid and cinnamic aldehyde, or derivatives thereof.
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- Process for preparing aryl-substituted piperidines
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A process for preparing a compound of formula (I): STR1 in which Ar represents an aryl or substituted aryl group and R3 represents an alkyl group, which comprises reducing a compound of formula (II): STR2 in which Ar and R3 are as defined for formula (I), and Hal represents a halogen atom.
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- Process for preparing aryl-piperidine carbinols and novel intermediates used in the process
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A process is disclosed for the preparation of a compound of formula (I): STR1 wherein Ar is aryl or substituted aryl and R3 is hydrogen, alkyl or aralkyl, which process comprises reducing a compound of formula (II): STR2 wherein Ar and R3 are as defined with respect to formula (I) and R4 is alkyl. Compounds of formula (I) are useful as chemical intermediates.
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