With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.25137-01-3,(R)-Ethyl piperidine-3-carboxylate,as a common compound, the synthetic route is as follows.
A mixture of 2-(3,3-bis(4-(trifluoromethyl)phenyl)-2-propen-1-yloxy)ethanol (25.0 g, 64 mmol) and triethylamine (16.2 g, 0.16 mol) in dry toluene (100 ml) kept under a nitrogen atmosphere was cooled to 10 C. and a solution of methanesulphonyl chloride (14.6 g, 0.13 mol) in dry toluene (100 ml) was added dropwise keeping the temperature below 10 C. When addition was complete the reaction mixture was stirred for 45 minutes at 5 C. and then for 30 minutes at 15 C. Water was added (100 ml) and the mixture was stirred at room temperature for 15 minutes. The phases were separated and the aqueous phase was extracted with two small portions of toluene. The combined organic extracts was washed with brine, dried over sodium sulphate and filtered. To the filtrate was added ethyl (R)-3-piperidine carboxylate (20.1 g, 0.13 mol) and potassium carbonate (22.1 g, 0.16 mol) and the mixture was heated at reflux temperature for 2 days and then stirred at room temperature for 2 days. The reaction mixture was filtered and the solvent evaporated in vacuo to give a residue which was dissolved into a mixture of ethyl acetate (125 ml) and water (75 ml). A 10% citric acid solution was added until pH 4 and the phases were separated. The organic phase was evaporated in vacuo to give a residue which was dissolved in toluene (150 ml). A mixture of a 34% citric acid solution (56 ml) and water (150 ml) was added and the phases were separated. The organic phase was extracted once more with a mixture of a 34% citric acid solution (20 ml) and water (50 ml). To the combined aqueous extracts was added ethyl acetate (150 ml) and excess of a 5% aqueous sodium bicarbonate solution. The phases were separated, the organic phase was dried over sodium sulphate and the solvent evaporated in vacuo to give 21.7 g (64%) of (R)-N-(2-(3,3-bis-(4-(trifluoromethyl)phenyl)-2-propen-1-yloxy)ethyl)-3-piperidinecarboxylic acid ethyl ester as an oil. TLC: rf=0.60 (SiO2; dichloromethane/methanol/acetic acid=20:2:1)., 25137-01-3
25137-01-3 (R)-Ethyl piperidine-3-carboxylate 185582, apiperidines compound, is more and more widely used in various fields.
Reference：
Patent; Novo Nordisk A/S; US5198451; (1993); A;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem