Hydrogen Bromide → 3,4-Dihydroxyphenyl propylamine

Participants

Reaction Steps

In general, reductive amination of 3,4-dimethoxyphenyl acetone (see FIG. 1) is carried out by using an appropriate amine (ammonia, methylamine, or ethylamine) in the presence of a reducing agent, preferably sodium borohydride or sodium cyanoborohydride, at a temperature from 0° C. to 25° C. to give the desired 3,4-dimethoxyphenyl propylamine (1A). The latter intermediate is then demethylated to give the 3,4-dihydroxyphenyl propylamine. Typically, demethylation of phenolic derivatives is carried out by reaction with boron tribromide in dichloromethane at −70° C. to room temperature. A variety of demethylation reactions are known in the art, for example, trimethylsilyl-iodide, sodium thioethoxide, potassium thiophenoxide, sodium cyanide in DMSO, aluminium tribromide in ethanethiol, and hydrobromic acid (Greene, T. and Wuts, P., “Protective groups in organic synthesis”, 2nd edition, Wiley-Intersciences, 1991). Preferably the demethylation of the 3,4-dimethoxyphenyl propylamine derivative (1A) is carried out in the presence of 48% HBr under reflux conditions for 3-4 hours to give 1B. The amino group of the 3,4-dihydroxyphenyl propylamine 1B is then protected.

Provenance & Evidence