Ethyl Acetate → 3-Morpholinecarbonitrile, 5-(4-methoxyphenyl)-5-methyl-

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Reaction Conditions

Reaction Steps

A solution of 160 mmol of lithium aluminium hydride (1M in hexane) in 750 ml of tetrahydro-furan is mixed at 0° C. with 7.8 ml of ethyl acetate and stirred at 0° C. for 2 hours. A solution of 20 mmol of 5-(4-methoxyphenyl)-5-methylmorpholin-3-one (Example 3i) in 250 ml of tetrahydrofuran is added dropwise to this solution, and the reaction mixture is stirred at 0° C. for 45 minutes. 600 ml of glacial acetic acid and then 120 mmol of a 4.5M aqueous potassium cyanide solution are added. The mixture is stirred at room temperature for 16 hours. The reaction mixture is diluted with 1M sodium bicarbonate solution and extracted with ethyl acetate-tetrahydrofuran 1:1 (3×). The combined organic phases are washed with brine, dried with sodium sulphate and evaporated. The title compound is obtained as a pale yellowish oil from the residue by flash chromatography (SiO2 60F). Rf=0.19 (CH2Cl2-MeOH 95:5); Rt=2.41 (gradient I).

Provenance & Evidence