Showing posts with label EP0436481. Show all posts
Showing posts with label EP0436481. Show all posts

Monday, 5 January 2015


Synthesis of 2-Cyanopiperidine 11
0.2 Mol of piperidine 7 in 130 ml dry ether was treated dropwise with 0.2 mol t-butylhypochlorite at 0°C. Stirring was continued at this temperature for 30 minutes. Three fourth of the solvent was evaporated in vacuo (t°<30°C) and the residual product (N-chloropiperidine 8 in ether) was triturated with 0.26 mol of 2N sodium methoxide in methanol. In most cases, a vigorous reaction started after several minutes. After this vigorous reaction ceased or after an additional 20 minutes at room temperature, the mixture was stirred under reflux for 45 minutes. The precipitate was then filtered and washed with little dry methanol, after which the solvent was removed in vacuo. The residual light-yellow solid (tripiperideine 10) [G.P. Claxton, L. Allen, J.M. Grisar, Org. Synth., Vol 56, 118 (1977)] was directly treated with aqueous hydrogen cyanide, prepared from 0.4 mol potassium cyanide and 0.4 mol 4N HCl (hood!). If necessary, some additional HCl 12N was added dropwise in order to acidify the solution ( water bath cooling). The mixture was stirred at ambient temperature for 1 h. Sodium hydroxide pellets were added under cooling till alkaline. The aqueous phase was extracted three times with dichloromethane, the organic phases were dried (MgSO₄) and evaporated in vacuo to leave a clear oil, which was distilled in vacuo to afford pure 2-cyanopiperidine 11 (65% yield), bp. 91-95°C/12 mmHg [Lit. bp. 90-92°C/12 mmHg; H. Böhme, H. Ellenberg, O.-E. Herboth, W. Lehners, Chem. Ber., vol.92, 1608 (1959)].