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3-chloro-5-hydroxy-benzonitrile is a pharmaceutical intermediate compound that can be used to synthesize Doravirine and MK-6186.

white powder

3-Chloro-5-hydroxybenzonitrile is a useful research chemical used in the preparation of (3-cyanophenoxy)pyrazoles as non-nucleoside HIV reverse transcriptase inhibitors.

General procedure for the synthesis of 3-chloro-5-hydroxybenzonitrile from 3-chloro-5-methoxybenzonitrile: 3-chloro-5-methoxybenzonitrile (7.0 g, 41.766 mmol) and 2,4,6-trimethylpyridine (100 mL) were added to a 250 mL three-necked flask. The reaction mixture was heated to 170 °C, followed by the addition of lithium iodide (16.76 g, 125.298 mmol) and the reaction was continued with stirring for 4 h at this temperature. The progress of the reaction was monitored by thin layer chromatography (TLC) and after confirming the complete consumption of raw materials, the reaction mixture was cooled to room temperature. The reaction was quenched with 10% aqueous hydrochloric acid and the reaction mixture was subsequently extracted with ethyl acetate (EtOAc). The organic phase was washed sequentially with water and saturated saline, dried over anhydrous sodium sulfate (Na2SO4) and filtered. The solvent was removed by concentration under reduced pressure to give a yellow oily crude product. Purification by silica gel column chromatography using ethyl acetate/hexane (10:90, v/v) as eluent gave 3-chloro-5-hydroxybenzonitrile (6.0 g, 94% yield) as a white solid.

[1] Patent: US2007/88015, 2007, A1. Location in patent: Page/Page column 22
[2] Patent: US2008/45511, 2008, A1. Location in patent: Page/Page column 17-18
[3] Patent: US2008/293664, 2008, A1. Location in patent: Page/Page column 15
[4] Patent: US2008/249151, 2008, A1. Location in patent: Page/Page column 20
[5] Patent: US2009/170856, 2009, A1. Location in patent: Page/Page column 20