1-Piperidinepropanol

Uses

Reactant in: Mitsunobu reaction of intramolecular nitrile oxide-alkene cycloadditions1 Suzuki-coupling2Reactant for synthesis of: Histamine H3 receptor antagonists3 Protein lysine methyltransferase G9a inhibitors4 Serotonin-4 receptors antagonists5 Checkpoint kinase Chk2 inhibitors6

Uses

1-Piperidinepropanol is used in preparation of Ionizable Amine lipids for lipid Nanoparticle compounds that deliver Nucleic Acids.

Synthesis

Step 2: Synthesis of 3-(piperidin-1-yl)propanol Anhydrous tetrahydrofuran (80 mL) was added to a dry three-necked flask and the reaction system was cooled to 0 °C. Lithium aluminum hydride (3.5 g, 93.4 mmol) was added to the flask in batches followed by slow dropwise addition of a tetrahydrofuran solution of methyl 3-(piperidin-1-yl)propionate (8.0 g, 46.7 mmol). After the dropwise addition was completed, the reaction mixture was gradually warmed up to room temperature and the reaction was continued with stirring for 2 hours. Upon completion of the reaction, the mixture was re-cooled to 0°C. Purified water (10 mL), 15% aqueous NaOH solution (10 mL) and purified water (30 mL) were added sequentially to the cooled mixture to quench the reaction. The resulting white solid was removed by filtration and the filtrate was concentrated to afford a yellow oily product, 3-(piperidin-1-yl)propanol (4.0 g), which could be used in subsequent steps without further purification.

References

[1] Tetrahedron, 2007, vol. 63, # 52, p. 12903 - 12911
[2] Patent: EP3181554, 2017, A1. Location in patent: Paragraph 0253