Uses
Reactant for synthesis of:• ;SMN protein modulators1• ;β-aryl and β-amino-substituted aliphatic esters by rhodium catalyzed tandem double bond migration/conjugate addition2• ;Nitroethylenediamines by nucleophilic ring opening of nitroimidazolidinone3• ;RhoA inhibitors for cardiovascular disease therapy4• ;Saccharin derived Mannich bases as antimicrobials and antioxidants5Reactant for one-pot reductive amination and Suzuki-Miyaura cross coupling of formyl aryl and heteroaryl MIDA boronates6
Synthesis
1. 4-Piperidinecarboxylic acid (1.29 g, 10.0 mmol) was dissolved in anhydrous ethanol (50 mL).
2. The reaction solution was cooled to 0 °C and thionyl chloride (2.91 mL, 40.0 mmol) was added slowly and dropwise.
3. The reaction mixture was stirred and heated to reflux for 48 hours.
4. After completion of the reaction, the solvent was evaporated under reduced pressure to give a yellow oily crude product.
5. The crude product was dissolved in ethyl acetate (EtOAc) and washed with 10% sodium hydroxide (NaOH) solution.
6. The organic layer was separated, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to give the clarified oily product ethyl 4-piperidinecarboxylate (1.48 g, 94% yield). 7. The product was analyzed by 1H NMR.
7. The product was characterized by 1H NMR (400 MHz, CDCl3) and mass spectrometry (ESI) to confirm the correct structure.
References
[1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 23, p. 7106 - 7109
[2] Letters in Organic Chemistry, 2015, vol. 12, # 4, p. 277 - 279
[3] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1983, vol. 22, # 5, p. 505
[4] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 18, p. 2693 - 2698
[5] European Journal of Medicinal Chemistry, 2000, vol. 35, # 7-8, p. 699 - 706
