[CH2:1]([NH:8][CH2:9][CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC(=C)[C:14]#[N:15].O.[CH3:18][C:19](C)([O-])C.[K+]>O1CCCC1>[CH2:1]([N:8]1[CH2:19][CH2:18][O:11][CH:10]([C:14]#[N:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
A one-litre reactor with mechanical stirring, cooled by an ice bath, was charged with N-benzylethanolamine (172.2 g; 1 equiv. available from Aldrich Chemical Company). 2-Chloroacrylonitrile (100 g; 1 equiv. available from Aldrich Chemical Company) was added dropwise over 2 minutes. The temperature was maintained between 23° C. and 29° C. by means of the ice bath and subsequently a water bath at 15° C. N-Benzylethanolamine was still detected on TLC after 4.5 h stirring. After one night stirring at room temperature (water bath), no N-benzylethanolamine was detectable by 1H NMR. The mixture was dissolved in tetrahydrofuran and transferred to a 2 L reactor cooled to −5° C. by ice/NaCl bath. The total volume of tetrahydrofuran was 1.35 L. Potassium tert-butoxide (148 g; 1.1 equiv.) was added by portions in 1 hour, keeping the reaction temperature at 0±2° C. After 1 hour post-stirring at 0° C., the mixture was quenched with saturated NaHCO3 (500 mL). The aqueous layer was extracted with diethyl ether (500 mL). Organic layers were dried on MgSO4 and evaporated to dryness. The title compound (149.8 g; 65%) was obtained after percolation of the 250 g dry residue on 1 kg of SiO2, eluting with the following gradient:
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