Triethylamine → 1,3-Dihydro-1-piperidin-4-yl-2H-benzimidazole-2-thione

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Reaction Steps

To a solution of 4-(2-amino-phenylamino)-piperidine-1-carboxylic acid ethyl ester (0.76 g, 2.9 mmol) and triethylamine (0.81 ml, 5.8 mmol) in methylene chloride (10 mL) at 0° C. was added a solution of thiophosgene (0.22 mL, 2.9 mmol) in methylene chloride (10 mL) at room temperature. The reaction mixture was stirred for 2 h then quenched with 1N sodium hydroxide. The organic phase was separated and dried over sodium sulfate, filtered and concentrated. The crude product (i.e.; 4-(2-thioxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid ethyl ester) was treated with 10% sodium hydroxide (10 mL) and refluxed for 4 h. The reaction was allowed to cool to room temperature and the aqueous layer was washed with ethyl ether (50 mL), acidified to pH<2 with 6N hydrochloric acid, washed with ethyl ether (50 ml) and filtered (to remove a small amount of precipitated solid). The aqueous layer was adjusted to pH 10 by slowly adding sodium carbonate and then cooled to 0° C. The solid that formed was collected by filtration to give 1-piperidin-4-yl-1,3-dihydro-benzoimidazole-2-thione (0.2 g).

Provenance & Evidence