With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.28697-07-6,N-Cbz-2-Piperidinecarboxylic acid,as a common compound, the synthetic route is as follows.
General procedure: (i) A solution of 2,6-difluorobenzoic acid (0.32 mol) in thionyl chloride (100 mL) was heated to reflux for 2 h. The resulting solution was concentrated and acid chloride intermediate was used in the next step without additional purification. To a solution of the acid chloride in anhydrous THF (100 mL) was added ammonium hydroxide (79 mL) at 0 C. After stirring at room temperature for 0.5 h, the reaction mixture was concentrated under reduced pressure. Then the reaction mixture was poured into cooled water (50 mL), extracted with ethyl acetate (100 mL x 3), and washed with brine (150 mL x 2). The organic layer was dried and concentrated to give the intermediate 2 in 90% yield which used in next step without purification. (ii) To a solution of 2,6-difluorobenzamide (0.28 mol) in concentrated sulfuric acid (90 mL) was added fuming nitric acid (12 mL) by dropwise under 0 C. The mixture was stirred for 2 h at room temperature. The pH was adjusted to 6 with 30% sodium hydroxide solution, then filtered and the filtrate was extracted with ethyl acetate (100 mL x 3),and washed with brine (150 mL x 2). The organic layer was dried and concentrated in vacuo to give the intermediate 3 as yellow solid in 91.40%yield. (iii) To a solution of 2,6-difluoro-3-nitrobenzamide (0.25 mol) in ethanol (300 mL) was added ammonium hydroxide (25 mL). The reaction mixture was stirred at room temperature overnight and the precipitate was collected by filtration, washed with isopropanol and dried in vacuum to give 4 31.5 g as yellow solid, yield 77.6%. (iv) A suspension of 2-amino-6-fluoro-3-nitrobenzamide (0.05 mol) in ethanol (100 mL) was reduced by hydrogen in the presence of palladium on carbon (10%, 1.00 g). After stirring at room temperature for 12 h, the reaction mixture was filtered. Solvent was removed under reduced pressure and the residue was subjected to silica gel column chromatography using dichloromethane/methanol (3:1) as eluent to give 55.00 g as light yellow solid, yield 58.9%. (v) To a solution of 3-pipecolinic acid (0.06 mol) and 2,3-diamino-6-fluorobenzamide (0.06 mol) in DMF (100 mL) was treated with PyBOP (0.06 mol) and N,N-diisopropylethylamine (0.18 mol).The reaction mixture was stirred at room temperature overnight. The solvent was removed using high vacuum. The residue was subjected to flash column chromatography using methylene chloride/methanol (30:1) to give the intermediate 6 as a white solid. The intermediate 6 was dissolved in glacial acetic acid (30 mL) and refluxed for 4 h until the reaction was complete (monitoring by TLC). The solvent was removed and the solid residue was purified by column chromatography using methylene chloride/methanol(80:1) as eluent to give pure 7a-7e in 50-72% yield. (vi) A solution of 7a-7e (25 mmol) in methanol (100 mL) was reduced with hydrogen in the presence of palladium on carbon (10%, 1.00 g). After stirring at room temperature for 12 h, the reaction mixture was filtered, and the filtrate was concentrated to give pure target compounds 8a-8e in 52-80% yield., 28697-07-6
The synthetic route of 28697-07-6 has been constantly updated, and we look forward to future research findings.
Reference£º
Article; Wang, Junwei; Wang, Xuyan; Li, Hui; Ji, Dezhong; Li, Yuyan; Xu, Yungen; Zhu, Qihua; Bioorganic and Medicinal Chemistry Letters; vol. 26; 16; (2016); p. 4127 – 4132;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem