http://www.google.com/patents/EP0436481A1?cl=en
Synthesis of 2-Cyanopiperidine 11
[0016]
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)].
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