Chemical Properties
white to light yellow crystal powder
Uses
(R)-(+)-N-Boc-2-piperidinecarboxylic Acid is a useful intermediate for agrochemical, pharmaceuticals and dye industries.
Uses
It is also applied as catalytic agent and petrochemical additive. It is also an important organic intermediate used in agrochemicals, pharmaceuticals and dyestuff fields.
reaction suitability
reaction type: Boc solid-phase peptide synthesis
Synthesis
The general procedure for the synthesis of (R)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid from di-tert-butyl dicarbonate and D-(+)-2-piperidinic acid was as follows: to a 1000 mL round-bottomed flask were added D-(+)-2-piperidinic acid (8.0 g, 0.062 mol), di-tert-butyl dicarbonate (14.8 g, 0.068 mol), sodium bicarbonate (26.04 g, 0.310 mol) and methanol (400 mL). The mixture was stirred and reacted at room temperature for 24 hours. Upon completion of the reaction, methanol was removed by distillation under reduced pressure. The residue was dissolved in water and subsequently washed three times with ether. The pH of the aqueous phase was adjusted to 2 with saturated potassium bisulfate solution and then extracted three times with dichloromethane. The organic phases were combined, washed three times with saturated saline, dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography with the eluent being a mixed solvent of petroleum ether/ethyl acetate/acetic acid, resulting in 12.48 g of white solid product in 87.8% yield. The product was characterized by 1H-NMR (400 MHz, DMSO) and EI-MS: 1H-NMR δ 12.71 (1H, s), 4.61 (1H, d, J = 28.8 Hz), 3.82 (1H, d, J = 12 Hz), 2.93 (1H, m), 2.06 (1H, s), 1.62 (3H, m), 1.39 (11H, m); EI-MS m/z: 229.1 [M]+.
References
[1] Journal of Medicinal Chemistry, 1998, vol. 41, # 4, p. 591 - 601
[2] Journal of Medicinal Chemistry, 1992, vol. 35, # 9, p. 1550 - 1557
[3] ChemMedChem, 2013, vol. 8, # 4, p. 577 - 581
[4] Patent: EP2805947, 2014, A1. Location in patent: Paragraph 0074-0075
[5] Patent: US2015/126500, 2015, A1. Location in patent: Paragraph 0127; 0128
