3,4-Dichlorobenzyl chloride → 2-[1-(3,4-Dichloro-benzyl)-piperidin-4-ylmethoxy]-6-fluoro-benzonitrile

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Reaction Steps

A mixture of 2-fluoro-6-(piperidin-4-ylmethoxy)-benzonitrile hydrochloride (240 mg; 0.89 mmol) (Example 126, Step 3) was heated with 3,4-dichlorobenzyl chloride (0.15 mL; 2.0 mmol) and triethylamine (0.3 mL; 2.0 mmol) to 50° C. for 16 hours. Reaction was cooled and quenched with dilute HCl and mixture extracted with ethyl acetate (2×20 mL). Combined organics washed with water, saturated sodium bicarbonate, brine and dried over Na2SO4. Crude material was purified by chromatography using 0.5-2% methanol/DCM gradient to afford 2-[1-(3,4-dichloro-benzyl)-piperidin-4-ylmethoxy]-6-fluoro-benzonitrile as a yellow oil. (280 mg; 73% yield).

Provenance & Evidence