Methyl isonipecotate may be used for the synthesis of a series of potent non-urea soluble epoxide hydrolase (sEH) inhibitors via high throughput screens.
4-Piperidinecarboxylic acid methyl ester is a an ester derivative of 4-piperidinecarboxylic acid used as a reagent in the organic synthesis of neurochemicals, antibacterials and other biologically active compounds.
Methyl piperidine-4-carboxylate is a reactant for C-2 arylation of piperidines through directed transition metal-catalyzed sp3 C-H activation. It is used as a reactant for synthesis of antitubercular agents, aminopyrazine inhibitors, orally available naphthyridine protein kinase D inhibitors and a scalable catalyst from asymmetric hydrogenation of sterically demanding aryl enamide.
Methyl isonipecotate can be obtained by the reduction of methyl isonicotinate in methanol with ruthenium at 100-150°C.
The general procedure for the synthesis of methyl 4-piperidinecarboxylate from the compound (CAS: 1262670-73-4) is as follows: the substrate (1 eq.) was dissolved in a minimal amount of water (about 15 eq.) containing CAN (20 mol%). The reaction mixture was transferred to dichloromethane and magnetically stirred. Acetic acid (10 equivalents) was added to the solution, followed by stirring at room temperature for the time specified in Table 2. Upon completion of the reaction, the solvent was removed by evaporation under reduced pressure and post-treated as follows. Method A: The solid residue was washed twice with petroleum ether to remove the by-product triphenylmethanol. Subsequently, the residue was dissolved in methanol and filtered through a short diatomaceous earth pad. The solvent was removed by evaporation under reduced pressure to obtain the free amine. Method B: Water and acetic acid were removed from the reaction mixture under vacuum. The residue was dissolved in anhydrous dichloromethane, followed by the addition of triethylamine (2.5 eq.) and acetic anhydride or benzoyl chloride (1.5 eq.). After completion of the reaction, the solvent was removed by evaporation. The residue was extracted twice with ethyl acetate. The organic layers were combined, washed sequentially with water and brine and finally dried over Na2SO4. The solvent was removed by evaporation under reduced pressure and the resulting residue was purified by silica gel column chromatography to afford the acylated amine.
[1] Tetrahedron Letters, 2011, vol. 52, # 1, p. 34 - 37
