Methyl iodide → (S)-3-Amino-1-{3-(4-methoxy-phenyl)-1-[2-(4-methoxy-phenyl)-ethyl]-propyl}-1-methyl-piperidinium chloride hydrochloride

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Reaction Steps

To (S)-piperidin-3-yl-carbamic acid tert-butyl ester (0.10 g) and 1,5-bis-(4-methoxy-phenyl)-pentan-3-one (254 mg, content ca. 88%; obtained by catalytic hydrogenation on platinum oxide pre-catalyst of bis(4-methoxybenzylidene)acetone, Pfaltz-Bauer) in CH2Cl2 is added Ti(OiPr)4 (0.22 mL). The mixture is stirred for 20 h, then NaBH4 (94 mg) is added in several portions. After 20 h MeOH is added and after 30 min volatiles are evaporated, the residue treated with EtOAc and filtered. The filtrate is concentrated in vacuo and purified by column chromatography (SiOH, cHex: EtOAc gradient of increasing polarity). Material thus obtained is allowed to react with iodomethane (2 eq.) in the presence of K2CO3 (1 eq.) in dimethylsulfoxide at 120° C. for 30 min under microwave irradiation. Volatiles are evaporated in vacuo, the residue is purified via preparative reverse phase HPLC. The carbamic acid tert-butyl ester group is removed using HCl in dioxane to give the title compound of content ca. 68%.

Provenance & Evidence