Synthesis
In a three-necked flask equipped with a stirrer, condenser tube and thermometer, add 2.4 g of m-hydroxybenzaldehyde dissolved in 40 mL of formic acid with stirring. The temperature was controlled to be below 60 °C and 4.2 g of hexahydropyridine was slowly added dropwise. After the dropwise addition was completed, the temperature was raised to 110 °C and the reaction was refluxed for 2 h (the progress of the reaction was monitored by thin layer chromatography). Upon completion of the reaction, the reaction solution was diluted with 150 mL of water and cooled to 15 °C. Decolorization was carried out by adding 0.1 g of activated carbon and filtered. The pH of the filtrate was adjusted with 12% ammonia to 8.5. allowed to stand and crystallized at 10 °C. The crystals were collected by filtration, washed with cold water and dried to give Intermediate III-1 (3-(1-piperidinylmethyl)phenol) 3.0 g as yellow crystals in 78% yield.
References
[1] Arzneimittel-Forschung/Drug Research, 1985, vol. 35, # 7, p. 1025 - 1029
[2] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 4, p. 989 - 994
[3] ChemMedChem, 2015, vol. 10, # 1, p. 83 - 93
[4] Patent: CN103626722, 2016, B. Location in patent: Paragraph 0049-0052
[5] Synthetic Communications, 1999, vol. 29, # 1, p. 15 - 20
