To a solution of 2-ethylsulfanyl-6-methyl-4-[(3R)-3-methyl-morpholin-4-yl]-benzamide (0.05 g, 0.17 mmol) in benzene-tetrahydrofuran (1:1) (2 ml) are added tetrabutylammonium hydrogensulfate (0.006 g, 0.017 mmol) and 50% sodium hydroxide solution (1.5 ml) at RT. 4-Chlorobenzyl bromide (0.038 g, 0.19 mmol) is added and the reaction mixture is slowly heated to 70° C. The reaction mixture is stirred at 70° C. for additional 45 min. After completion of the reaction (monitored by TLC), the organic layer is separated and the aqueous layer is extracted with ethyl acetate (2×20 ml). The organic layer is washed with water (20 ml), brine (20 ml), dried over anhydrous sodium sulfate and evaporated to get the crude product, which is purified by column chromatography (silica gel, 8% acetone/hexane) to yield N-[(4-chlorophenyl)-methyl]-2-ethylsulfanyl-6-methyl-4-[(3R)-3-methyl-morpholin-4-yl]-benzamide (example 4) (0.023 g, 0.055 mmol, 32%). [M+H]+ 419.2.
