1-Octanethiol → 4-{1-[2-(4-Cyanophenyl)ethyl]-4-hydroxypiperidin-4-ylmethoxy}benzoic acid

Participants

Reaction Steps

To a solution of n-octanethiol (2.04 g) in a mixture of anhydrous tetrahydrofuran (10 mL) and anhydrous hexamethylphosphoric triamide (HMPA) (5 mL), a 1.59 M solution of n-butyl lithium in hexane (8.74 mL) was added dropwise under cooling with ice-water under nitrogen atmosphere. After stirring at the same temperature for fifteen minutes, a solution of the compound (2.50 g) obtained in Example 13 in a mixture of anhydrous tetrahydrofuran (10 mL) and anhydrous HMPA (5 mL) was added dropwise thereto over ten minutes, followed by stirring at the same temperature for thirty minutes and further stirring at room temperature for seventeen hours. After the completion of reaction, the reaction mixture was mixed with an ice water (20 mL) under cooling with ice-water and was washed with ethyl acetate (25 mL×2). Small portions of 3 N hydrochloric acid were gradually added to the aqueous layer with stirring under cooling with ice-water, to adjust the pH of the mixture to 5.6. The precipitated crystals were collected by filtration and were sequentially washed with water and ethanol. The resulting crystals were suspended in a mixture of methanol (50 mL) and water (10 mL), followed by heating under reflux for thirty minutes. After standing to cool, the crystals were collected by filtration and were washed with methanol, and dried under reduced pressure to yield the titled compound (1.83 g) as crystals.

Provenance & Evidence