WO 2007/119247 offers a truly wonderful synthesis that runs at RT using non-toxic solvents and very safe precursors.
A closer look reveals that a phenyl-benzyl ketone is reacted with methylamine hydrochloride which is freebased in situ at RT. The hydroxide also removes all of the water produced by the imine formation driving it to the right. So replace each mole of methylamine hydrochloride with isopropylamine hydrochloride. Plain NaBH4 reduces imine to amine.
Believe me, I really did read through some 150 patents to find this because I knew that whoever was making sertraline from sertralone would not want to use TiCl4, nasty, solvents or smelly precursors.
I am sure others will have a better idea than me. It's attractive because it runs at RT, uses methanol as solvent, KOH not only to freebase amine but also to remove H2O.... for someone working in their own space, ideal.
Without a doubt, isophenidine is the best of the series and while the hydrochloride IS soluble, the sulfate is much, much more soluble. I've snorted the hydrochloride, sulfate and phosphate and all 3 were OK as far as we could tell, we had to agree that it IS a LOT like MXE.... apart from the fact that it can be made from cheap, common precursors.
A closer look reveals that a phenyl-benzyl ketone is reacted with methylamine hydrochloride which is freebased in situ at RT. The hydroxide also removes all of the water produced by the imine formation driving it to the right. So replace each mole of methylamine hydrochloride with isopropylamine hydrochloride. Plain NaBH4 reduces imine to amine.
Believe me, I really did read through some 150 patents to find this because I knew that whoever was making sertraline from sertralone would not want to use TiCl4, nasty, solvents or smelly precursors.
I am sure others will have a better idea than me. It's attractive because it runs at RT, uses methanol as solvent, KOH not only to freebase amine but also to remove H2O.... for someone working in their own space, ideal.
Without a doubt, isophenidine is the best of the series and while the hydrochloride IS soluble, the sulfate is much, much more soluble. I've snorted the hydrochloride, sulfate and phosphate and all 3 were OK as far as we could tell, we had to agree that it IS a LOT like MXE.... apart from the fact that it can be made from cheap, common precursors.