Dimethylamine → 3-Hydroxybenzaldehyde

Participants

Reaction Steps

A portion of (trans,trans,trans,trans)-4-(3-fluoro-2-methylphenyl)-2,6-dimethylpiperidine-3,5-diyl)bis((3-methoxyphenyl)methanone (200 mg, 0.41 mmol), 1-bromo-2-chloroethane (0.1 mL, 0.6 mmol), and diisopropylethylamine (0.1 mL, 0.6 mmol) in N-methylpyrrolidone (1 mL) was heated to 150° C. in a microwave oven for 30 min. The mixture was diluted in EtOAc, washed with saturated NaHCO3, dried over Na2SO4, and evaporated to dryness. The residue was resuspended in dimethylamine solution (0.2 mL, 2 M in THF, 0.4 mmol) and NMP (1 mL), and heated to 120° C. for 30 min. The solution was diluted with EtOAc, washed with saturated NaHCO3, dried over Na2SO4, and concentrated under vacuum. This residue was redissolved in dichloromethane (10 mL) and treated with boron tribromide (2 mL, 1 M in dichloromethane, 2 mmol) at room temperature. After stirring 30 min, the reaction was quenched with methanol and the solvents removed under vacuum. Purification of the crude product by reverse phase chromatography (HPLC, C18) using acetonitrile and water with 0.1% TFA buffer gave pure desired (trans,trans,trans,trans)-1-(2-(dimethylamino)ethyl)-4-(3-fluoro-2-methylphenyl)-2,6-dimethylpiperidine-3,5-diyl)bis((3-hydroxyphenyl)methanone (5.3 mg, 2.4% yield) (characterized by LCMS and 1H NMR, LRMS (M+H+) m/z=533.2.

Provenance & Evidence