With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.163765-44-4,(R)-1-Boc-3-Methylpiperazine,as a common compound, the synthetic route is as follows.
Preparation 11 (R)-4-(5-Carboxy-pyridin-2-yl)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester A mixture of 6-fluoronicotinic acid (150 g, 1.063 mol) and (R)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (234.2 g, 1.169 mol) in tetrahydrofuran (1.75 L) was cooled to -40 C. and then 2 M isopropylmagnesium chloride in tetrahydrofuran (1.196 L, 2.39 mol) was added slowly maintaining the temperature less than -20 C. The reaction mixture was slowly warmed to RT, stirred at RT for 4 h and then 1N HCl (1.75 L) and water (1.175 L) were added. The reaction mixture was extracted with ethyl acetate (4 L). The organic phase was evaporated to provide crude solid (534 g). To the crude solid was added acetone (2 L) and water (200 mL). The resulting reaction mixture was heated to 50 C. and then water (2.8 L) was added slowly. Seed crystals from a previous run at smaller scale were added after ?1 L of water. The reaction mixture was cooled to 20 C. over 3 h, stirred at 20 C. overnight and filtered. The solid was washed with 2:3 acetone:water (2*500 mL) and dried under vacuum to provide the title compound (329 g, 96% yield) as an off-white solid. HPLC Method A: Retention time 9.73 min., 163765-44-4
The synthetic route of 163765-44-4 has been constantly updated, and we look forward to future research findings.
Reference：
Patent; LONG, Daniel D.; MCKINNELL, Robert Murray; JIANG, Lan; LOO, Mandy; LEPACK, Kassandra; VAN ORDEN, Lori Jean; OGAWA, Gavin; HUANG, Xiaojun; ZHANG, Weijiang; US2013/115194; (2013); A1;,
Piperazine – Wikipedia
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