[H-].[Na+].[Cl:3][C:4]1[CH:12]=[CH:11][C:7]([CH2:8][C:9]#[N:10])=[CH:6][CH:5]=1.Cl[CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.[OH-].[Na+]>CN(C=O)C.C1(C)C=CC=CC=1>[Cl:3][C:4]1[CH:12]=[CH:11][C:7]([CH:8]([CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[C:9]#[N:10])=[CH:6][CH:5]=1To a flask was added 1.4 g. (0.033 mole) of a 55% oil dispersion of sodium hydride. After washing the sodium hydride with hexane to remove the mineral oil, 20 ml. of a 2 to 1 mixture of toluene and DMF was added followed by the slow addition of 5.0 ml. (0.033 mole) of 4-chlorobenzyl cyanide. The resulting deep burgundy solution was stirred for one hour. The hydrochloride salt of 4-(2-chloroethyl)morpholine, 6.4 g. (0.033 mole), was neutralized with sodium hydroxide in a separate vessel and the resulting 4-(2-chloroethyl)morpholine free base was dissolved in 10 ml. of a 2 to 1 mixture of toluene and DMF. The free base solution was added slowly to the 4-chlorobenzyl cyanide solution at 0° C. and the reaction stirred at room temperature for two days. The reaction was poured into ice water and the organic layer extracted with ether. The ether extract was washed twice with 10% aqueous hydrochloric acid, the aqueous material made basic using concentrated ammonium hydroxide, and the desired free base material extracted into ethyl acetate. The ethyl acetate solution was dried, filtered, and concentrated. The crude product was purified by flash chromatography to give 3.7 g. (42% yield) of 2-(4-chlorophenyl)-4-(4-morpholinyl)butyronitrile as a yellow oil.
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