反应详情

The present invention relates to a method of resolving an important intermediate of Ivabradine i.e., 4,5-dimethoxy-1-(methyl-amino-methyl)-benzocyclobutane (II) (an amine intermediate, a racemate), comprising the step of reacting a resolving agent with said intermediate to obtain the corresponding salt in an alcoholic solvent or an alcoholic aqueous solution, and crystallizing the corresponding salt to obtain the end product (1S)-4,5-dimethyloxy-1-(methylaminomethyl)-benzocyclobutane of formula (I), wherein said resolving agent is dibenzoyl-L-tartaric acid (LDBTA), dibenzoyl-D-tartaric acid (DDBTA), di-p-toluoyl-L-tartaric acid (LDTTA) or di-p-toluoyl-D-tartaric acid (DDTTA), and preferably di-p-toluoyl-L-tartaric acid, or di-p-toluoyl-D-tartaric acid.

1. customto obtain the corresponding salt in an alcoholic solvent
2. customan alcoholic aqueous solution, and crystallizing the corresponding salt