p-Toluenesulfonic acid → 2,2,2-trichloro-ethyl (3RS,4RS)-4-[3-(2-hydroxy-ethoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate

Participants

Reaction Steps

From 1-benzyl-4-(3-methoxy-phenyl)-piperidin-3-ol by cleavage of the methyl ether (RS)- and (SR)-methoxy-phenyl-acetate boron tribromide in methylene chloride there was obtained (3RS,4RS)-1-benzyl-4-(3-hydroxy-phenyl)-piperidin-3-ol as a pale yellow solid; MS: 283 (M)+. Alkylation with rac.-2-(2-iodo-ethoxy)-tetrahydro-pyran in the presence of potassium carbonate gave a mixture of (3RS,4RS)-1-benzyl-4-[3-[2-[(RS)- and -[(SR)-tetrahydro-pyran-2-yloxy]-ethoxy]-phenyl]-piperidin-3-ol as a colourless oil; MS: 410 (M-H)+. By subsequent alkylation with 2-bromomethylnaphthalene in an analogous manner to that described in Example 22(i) there was obtained a mixture of (3RS,4RS)-1-benzyl-3-(naphthalen-2-ylmethoxy)-4-[3-[2-[(RS)- and -[(SR)-tetrahydro-pyran-2-yloxy]-ethoxy]-phenyl]-piperidine as a colourless oil; MS: 552 (M)+. Then, by cleavage of the benzyl group using 2,2,2-trichloroethyl chloroformate and potassium carbonate in an analogous manner to that described in Example 25(a) there was obtained a mixture of 2,2,2-trichloroethyl (3RS,4RS)-3-(naphthalen-2-ylmethoxy)-4-[3-[2-[(RS)- and -[(SR)-tetrahydro-pyran-2-yloxy]-ethoxy]-phenyl]-piperidine-1-carboxylate; Rf : 0.60 (SiO2, methylene chloride:ethyl acetate=2:1). By subsequent cleavage of the THP group using p-toluenesulphonic acid there was obtained 2,2,2-trichloro-ethyl (3RS,4RS)-4-[3-(2-hydroxy-ethoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate. Finally, by reaction with pyridine-2-carbonyl azide in an analogous manner to that described in Example 24(m) there was obtained 2,2,2-trichloro-ethyl (3RS,4RS)-3-(naphthalen-2-ylmethoxy)-4-[3-(2-pyridin-2-ylcarbamoyloxy-ethoxy]-phenyl]-piperidine-1-carboxylate; Rf : 0.45 (SiO2, methylene chloride:ethyl acetate=9:1).

Provenance & Evidence