A mixture of intermediate 19 (0.081 mol) in CH3OH (300 ml) and 2-propanol in HCl (30 ml) was stirred and refluxed for 2 hours. The solvent was evaporated The residue was taken up in water/DIPE and the mixture was separated into its layers. The aqueous layer was alkalized with NaOH and CH2Cl2 was added. The combined organic layer was washed with water, dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). Two pure fractions were collected and their solvents were evaporated, yielding 3 g of fraction 1,2 g fraction 2 and 2.5 g of (±)-N-[1-[2-(phenylmethyl)-4-piperidinyl]-4-phenyl-4-piperidinyl]acetamide (intermediate 20). Fraction 1 was dissolved in 2-propanol and converted into the hydrochloric acid salt (1:2) with HCl/2-propanol. The precipitate was filtered off and dried, yielding 0.24 g (±)-cis-N-[1-[2-(phenylmethyl)-4-piperidinyl]-4-phenyl-4-piperidinyl]acetamide dihydrochloride. dihydrate (intermediate 21). Intermediate 20 was repurified by column chromatography oversilica gel (eluent: CH2Cl2/(CH3OH/NH3)95/5). The pure fractions were collected and the solvent was evaporated The residue was dissolved in 2-propanol and converted into the hydrochloric acid salt (1:2) with HCl/2-propanol. The precipitate was filtered off and dried, yielding 0.44 g of (±)-trans-N-[4-phenyl-1-[2-(phenylmethyl)-4-piperidinyl]-4-piperidinyl]-4-piperidinyl]acetamide dihydrochloride dihydrate (intermediate 22). Less pure fractions (20 g) were repurified by HPLC over silica gel (eluent: CH2Cl2/(CH3OH/NH3)95/5). Two pure fraction groups were collected and their solvent was evaporated, yielding 6.5 g (±)-cis-N-[4-phenyl-1-[2-(phenylmethyl)-4-piperidinyl]-4-piperdinyl]acetamide (intermediate 23) and 7.2 g (±)-trans-N-[1-[2-(phenylmethyl)-4-piperidinyl]-4-phenyl-4-piperidinyl]acetamide (intermediate 24).
