Uses
Methyl (2S)-Piperidine-2-carboxylate Hydrochloride can be useful in the preparation of Thyrotropin-releasing hormone (TRH) analogs, preparation of (arylsulfonyl)(amidino)phenylalanine piperidinamides as matriptase inhibitors, stereoselective synthesis of protected peptides containing anti β-hydroxy tyrosine, preparation of analogs of endogenous neuropeptide cycloprolylglycine, and preparation of promysalin analogs. It can also be useful in the preparation of molecular switches within ADX-47273 mGlu5 PAM scaffold that modulate modes of pharmacology to afford mGlu5 modulators.
Synthesis
Under argon protection, (S)-piperidine-2-carboxylic acid (10.00 g, 77.46 mmol) was dissolved in methanol (200 ml) and cooled to 0°C. Subsequently, thionyl chloride (15.0 ml, 205.61 mmol) was slowly added. The reaction mixture was stirred at 0 °C for 30 min and then heated to reflux overnight. After completion of the reaction, the solvent was removed by evaporation and the residue was recrystallized from ethanol to afford methyl (S)-piperidine-2-carboxylate hydrochloride (9.90 g, 92% yield). Mass spectrometry (EIMS) showed m/z 144.1 ([M+H]+).
References
[1] Journal of Medicinal Chemistry, 2005, vol. 48, # 23, p. 7333 - 7342
[2] Chemistry - A European Journal, 2010, vol. 16, # 25, p. 7547 - 7553
[3] Patent: WO2015/28850, 2015, A1. Location in patent: Page/Page column 88
[4] Tetrahedron Letters, 1991, vol. 32, # 49, p. 7183 - 7186
[5] Patent: WO2014/19344, 2014, A1. Location in patent: Paragraph 00601
