Dimethylamine → 3-Hydroxybenzaldehyde

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.

1. washwashed with saturated NaHCO3
2. dry with materialdried over Na2SO4
3. customevaporated to dryness
4. washwashed with saturated NaHCO3
5. dry with materialdried over Na2SO4
6. concentrationconcentrated under vacuum
7. dissolutionThis residue was redissolved in dichloromethane (10 mL)
8. customthe reaction was quenched with methanol
9. customthe solvents removed under vacuum
10. customPurification of the crude product by reverse phase chromatography (HPLC

ORD record

ord-49fbcfa6b5a34abc9f99b389f39be171

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07572814B2