Method for preparing single isomer of 1-(1-(2-benzylphenoxy)propan-2-yl)-2-methylpiperidine in high-purity

A method for preparing a single isomer from a mixture of 2 or more types of isomers among 4 types of isomers of 1-(1-(2-benzylphenoxy)propan-2-yl)-2-methylpiperidine having two chirality centers, as a phosphate with a purity of 99% or more, the method comprising:

• Step 1 of preparing a mixture comprising 2 or more types of isomers of 1-(1-(2-benzylphenoxy)propan-2-yl)-2-methylpiperidine comprising an isomer of interest by reacting (R)- or (S)-1-(2-benzylphenoxy)propan-2-ol in which a hydroxyl group is activated with a racemic mixture of 2-methylpiperidine;
• Step 2 of obtaining a hydrochloride of 1-(1-(2-benzylphenoxy)propan-2-yl)-2-methylpiperidine in a solid form by treating a solution in which the mixture comprising 2 or more types of 1-(1-(2-benzylphenoxy)propan-2-yl)-2-methylpiperidine is dissolved in acetone with hydrochloric acid;
• Step 2-a of obtaining a hydrobromide of the compound by recrystallizing a filtrate recovered from Step 2 with hydrobromic acid once or more than once, optionally, in the case where the isomer of interest is an (S,S) form or an (R,R) form, and
• Step 3 of substituting the hydrochloride or hydrobromide of the compound obtained in the previous step with a phosphate of the compound by adding phosphoric acid to a solution in which the hydrochloride or hydrobromide of the compound is dissolved in ethanol.