Synthesis
Thionyl chloride (1.81 mL, 24.8 mmol) was slowly added dropwise to a cooled suspension of 7-aminoheptanoic acid (1.8 g, 12.4 mmol) in methanol (30 mL) under stirring conditions, and the reaction temperature was controlled to be maintained between -5°C and -10°C. The reaction was carried out by stirring. After the thionyl chloride drop was completed, the reaction mixture was gradually warmed up to room temperature with continuous stirring overnight. Upon completion of the reaction, the solvent was removed by vacuum concentration to give a white solid product. The solid was ground twice with ether to give a final 2.38 g of 7-aminoheptanoic acid methyl ester hydrochloride (1:1) (5) as a white solid (theoretical yield 4.8 g, 100% yield).
References
[1] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 9, p. 2809 - 2812
[2] Patent: WO2011/91213, 2011, A2. Location in patent: Page/Page column 76-78
[3] Patent: WO2013/13113, 2013, A2. Location in patent: Page/Page column 72-73
[4] Journal of Medicinal Chemistry, 2006, vol. 49, # 20, p. 6094 - 6103
[5] Journal of Medicinal Chemistry, 2018, vol. 61, # 6, p. 2589 - 2603
