Diclofensine (Ro 8-4650) was developed by Hoffmann-La Roche in the 1970s[1] in the search for a new antidepressant.

[2] Diclofensine is a stimulant drug which acts as a triple monoamine reuptake inhibitor,[3][4] primarily inhibiting the reuptake of dopamine[5] and norepinephrine,[6] with affinities (Ki) of 16.8 nM, 15.7 nM, and 51 nM for DAT, NET, and SERT (dopamine, norepinephrine and serotonin transporters), respectively.

Reduction of this Schiff-base intermediate with sodium borohydride gives (3-methoxybenzyl)methylamine [41789-95-1] (2).

Reduction of the benzoyl ketone with sodium borohydride gives the alcohol [802051-24-7] (5).

Acid catalyzed intramolecular cyclization then completes the synthesis of the 4-aryl-THIQ derivative, diclofensine (6).