1-Chloro-4-(chloromethyl)benzene → HCID 53361740, compound

Participants

Reaction Steps

To a solution of (E)-3-{3-chloro-4-[(5-hydroxypyridin-2-yl)oxy]-5-methylphenyl}-1-(4-{4-[2-(4-methylphenoxy)ethyl]benzyl}piperazin-1-yl)prop-2-en-1-one (479 mg) and p-chlorobenzyl chloride (129 mg) in DMF (5.0 mL) was added NaH (41.6 mg, 60% in mineral oil) at 0° C. Then the reaction mixture was stirred over night at room temperature. The reaction mixture was quenched by addition of saturated aqueous NH4Cl, and extracted with AcOEt. The organic layer was washed with water and saturated aqueous NaCl, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=1/0 to 9/1) to afford (E)-3-[3-chloro-4-({5-[(4-chlorobenzyl)oxy]pyridin-2-yl}oxy)-5-methylphenyl]-1-(4-{4-[2-(4-methylphenoxy)-ethyl]benzyl}piperazin-1-yl)prop-2-en-1-one (507 mg) as a colorless amorphous. To a solution of that amorphous (507 mg) in EtOH (10 mL) was added 6 M aqueous HCl (0.129 mL) at room temperature, then the reaction mixture was stirred for 3 hours. The reaction mixture was filtered off, and the precipitate was dried at 50° C. under reduced pressure to afford (E)-3-[3-chloro-4-({5-[(4-chlorobenzyl)oxy]pyridin-2-yl}oxy)-5-methylphenyl]-1-(4-{4-[2-(4-methylphenoxy)ethyl]benzyl}piperazin-1-yl)prop-2-en-1-one hydrochloride (486 mg) as a colorless crystal.

Provenance & Evidence