Water → 4-Benzylmorpholine-2-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A one-litre reactor with mechanical stirring, cooled by an ice bath, is 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) is added dropwise over 2 minutes. The temperature is maintained between 23° C. and 29° C. by means of the ice bath and subsequently a water bath at 15° C. After one night stirring at room temperature (water bath), the mixture is dissolved in tetrahydrofuran and transferred to a 2 L reactor which is cooled to −5° C. by ice/NaCl bath. The total volume of tetrahydrofuran is 1.35 L. Potassium tert-butoxide (148 g; 1.1 equiv.) is added by portions over 1 hour, keeping the reaction temperature at 0±2° C. After 1 hour post-stirring at 0° C., the mixture is quenched with saturated NaHCO3 (500 mL). The aqueous layer is extracted with diethyl ether (500 mL). Organic layers are dried over MgSO4 and evaporated to dryness. The title compound (149.8 g; 65%) is obtained after percolation of the 250 g dry residue on 1 kg of SiO2, eluting with the following gradient:

Provenance & Evidence