75240-91-4

Upstream product

• 86562-23-4 (+/-)-3-(3-methoxyphenyl)-N-n-propylpiperidine 
• 79412-41-2 3-(3-methoxyphenyl)-N-n-propylpiperidine hydrobromide 
• 110174-88-4 3-<3-(benzyloxy)phenyl>-N-propylpiperidine 
• 906360-22-3 3-(3-methoxyphenyl)-1-p-toluenesulfonylpiperidine 
• 79601-21-1 3-(3-methoxyphenylpiperidine) 
• 220384-68-9 1-(p-toluenesulfonyl)-piperidin-3-ol 
• 220384-55-4 1-(p-toluenesulfonyl)-piperidin-3-one 
• 79987-71-6 2-(3-methoxyphenyl)glutaric acid 
• 79987-73-8 2-(3-methoxyphenyl)-N-propylglutarimide 
• 79987-86-3 2-(3-Methoxy-phenyl)-5-(tetrahydro-pyran-2-yloxy)-pentanenitrile 
• 107623-21-2 1-(benzyloxy)-3-iodobenzene 
• 4373-67-5 3-(3-methoxyphenyl)pyridine 
• 53385-78-7 1-propyl-1,2,3,6-tetrahydropyridine 
• 626-02-8 3-Iodophenol 

Downstream Products

• 126113-07-3 2-hydroxy-4-(1-propyl-3-piperidinyl)benzaldehyde 
• 110174-84-0 3-<3-<<2-(carbobenzoxyamino)propanoyl>oxy>phenyl>-N-propylpiperidine 
• 85966-89-8 preclamol 
• 85976-54-1 (+)-preclamol 
• 126088-50-4 2-(2-propenyl)-5-(1-propyl-3-piperidinyl)phenol 
• 126088-48-0 2-methyl-5-(1-propyl-3-piperidinyl)phenol 
• 126088-49-1 2-(2-propenyl)-3-(1-propyl-3-piperidinyl)phenol 
• 126088-57-1 3-<3-(2-propenyloxy)phenyl>-1-propylpiperidine 

Relevant academic research and scientific papers

AN EFFICIENT RESOLUTION OF 3-PPP AND ASSIGMENT OF THE ABSOLUTE CONFIGURATION

(+/-)-3-PPP has been resolved by means of (+)- and (-)-2,2'-(1,1'-binaphtyl)phosphoric acid (BNPPA) in high optical purity; (+)-3-PPP has been assigned the R configuration on the basis of a single crystal X-ray analysis.

Synthesis of 3,3-Dichloropiperidines and Further Functionalization via Pd-Catalyzed Cross-Coupling Reactions of the Dichloromethylene Moiety

A new synthetic methodology for the functionalization of the dichloromethylene moiety in 3,3-dichloropiperidines via Pd-catalyzed cross-coupling reactions is reported. A range of 3,3-dichloropiperidines was synthesized via a hydride induced cyclization of α,α,δ-trichloroaldimines or an indium(III) triflate catalyzed alkynylation/cyclization procedure of α,α,δ-trichloroaldimines. Subsequently, a dehydrochlorination followed by a cross-coupling with the thus formed vinylic chloride was envisioned. The non-alkynylated 3,3-dichloropiperidines could be regioselectively eliminated and by careful choice of solvent and base both of the two regioisomeric vinyl chlorides could be exclusively formed. Palladium-catalyzed Suzuki cross-coupling of the thus formed 5-chloro-1,2,3,6-tetrahydropyridines led to C3-substituted 1,2,3,6-tetrahydropyridines, which could be easily reduced to 3-substituted piperidines, generating therapeutic agent (±)-Preclamol for example. The 2-alkynyl-3,3-dichloropiperidines were regioselectively eliminated giving the cyclic enamine, which was subsequently cross-coupled in one-pot. The presence of the alkynyl function, in this case, clearly directs elimination towards enamine structures. Hydrogenation of the resulting, unstable 2-alkynyl-3-substituted-1,2,3,4-tetrahydropyridines, yields stable 2,3-disubstituted piperidines.

Decarboxylative Negishi Coupling of Redox-Active Aliphatic Esters by Cobalt Catalysis

A cobalt-catalyzed decarboxylative Negishi coupling reaction of redox-active aliphatic esters with organozinc reagents was developed. The method enabled efficient alkyl–aryl, alkyl–alkenyl, and alkyl–alkynyl coupling reactions under mild reaction conditions with no external ligand or additive needed. The success of an in situ activation protocol and the facile synthesis of the drug molecule (±)-preclamol highlight the synthetic potential of this method. Mechanistic studies indicated that a radical mechanism is involved.

Optimizing the Mizoroki–Heck reaction of cyclic allyl amines: Gram-scale synthesis of preclamol without protecting groups

Though a widely used metal-catalyzed cross-coupling process, the Mizoroki–Heck (MH) reaction can be a capricious transformation. This is particularly true for oxidation-prone alkene substrates containing ligating heteroatoms, as in the case of N-alkyl tetrahydropyridines, whose MH reactions have been underexplored due to the many side reactions that hamper the process. Since the products of tetrahydropyridine Heck reactions are direct precursors to potent pharmacophores, and therefore of commercial value, this is a significant drawback. We report here the results of our study designed to deliver an optimized, scalable MH procedure for N-alkyltetrahydropyridines and its exemplification in a gram-scale synthesis of the drug substance preclamol.

Cobalt-Catalyzed Cross-Coupling of 3- and 4-Iodopiperidines with Grignard Reagents

A cobalt-catalyzed cross-coupling between 3- and 4-iodopiperidines and Grignard reagents is disclosed. The reaction is an efficient, cheap, chemoselective, and flexible way to functionalize piperidines. This coupling was used as the key step to realize a short synthesis of (±)-preclamol. Some mechanistic investigations were conducted that highlight the formation of radical intermediates. Scaffold synthesis: A cobalt-catalyzed cross-coupling between iodopiperidines and Grignard reagents is reported (see scheme; PG=protecting group). A large variety of 3- and 4-substituted piperidines were synthesized and the method was applied to a short synthesis of (±)-preclamol. This work constitutes one of the rare examples of cross-couplings involving 3-halogeno piperidines.

Ligand-promoted C3-selective arylation of pyridines with Pd catalysts: Gram-scale synthesis of (±)-preclamol

The first example of Pd-catalyzed, C3-selective arylation of unprotected pyridines has been developed by employing a catalytic system consisting of Pd(OAc)2 and 1,10-phenanthroline. This protocol provides an expeditious route to an important class of 3-arylpyridines and 3-arylpiperidines frequently found in bioactive compounds. A brief synthesis of the drug molecule (±)-preclamol is also reported.

Concise synthesis of 3-arylpiperidines

We present an easy and straightforward synthesis of 3-arylpiperidines by Grignard addition of piperidin-3-one with different arylmagnesium bromide reagents and acidic dehydroxylation of the resulting tertiary alcohol with the combination of triethylsilane and boron trifluoride etherate. This facile strategy was further used to synthesize preclamol. A highly regioselective dehydration of 3-arylpiperidin-3-ol with boron trifluoride etherate was investigated for preparing 3-aryl-1,4,5,6-tetrahydropyridine skeleton. A novel selenium dioxide mediated dihydroperoxidation of 3-aryl-1,4,5,6-tetrahydropyridine was also examined.

AN EFFICIENT AND INEXPENSIVE RESOLUTION OF THE POTENT DOPAMINERGIC SUBSTANCE 3-(3-HYDROXYPHENYL)-N-(1-PROPYL)-PIPERIDINE (+/-)-3-PPP

A new convenient and inexpensive resolution of the dopaminergic agonist (+/-)-3-PPP is described.

Process for making m-hydroxyphenyl substituted compounds

m-Hydroxyphenyl substituted compounds of formula STR1 where R is an organic radical and R1 is hydroen or an organic radical are prepared by dehydrohalogenating a compound of formula STR2 (where X is chlorine or bromine, and R and R1 have the above meanings). Preferred novel starting materials of formula (II) are of the formula STR3 (where R1 and X are as above, n is 2,3 or 4, R2 is hydrogen or lower alkyl and R3 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl(lower)alkyl or aryl(lower)alkyl).