Patent ID: 8058436

Claim:
A method for the preparation of an enantiomer of mirtazapine comprising less than 10% of the other enantiomer, the method comprising a ring closure reaction of a compound of formula (II) wherein X is a leaving group, the reaction comprising treatment with an acid, wherein the mirtazapine with enantiomeric excess is formed by the ring closure reaction of an R- or S-enantiomer of the compound of formula (II) by treatment with an acid or acid/solvent combination selected from the group consisting of a) polyphosphoric acid in the absence of a solvent and wherein the weight ratio between polyphosphoric acid and the compound according to formula II is less than 2.5:1; b) polyphosphoric acid in the presence of the solvent N-methylpyrrrolidinone or dimethylformamide; and c) phosphorus pentoxide in the presence of the solvent N-methylpyrrolidinone and dimethylformamide.