Synthesis Of Cis(trans)-3-(tert-butyloxycarbonyl) Aminocyclohexanol

In this thesis, we studied the synthesis of cis(trans)-3-(tert-butyloxycarbonyl) aminocyclohexanol.1. Synthesis of cis-3-(tert-butyloxycarbonyl)aminocyclohexanol.Amides had been used as nucleophiles for aza-Michael additions to 2-cyclohexen-l-one catalyzed by Bi(NO)3·5H2O or DIEA. Then reduction of the Michael products with reducing agents gave cis-1,3-aminoalcohols with in good selectivity(Figure 1). Separation of cis3b was carried out by fractional crystallization with diethyl ether.The substrate 3d was released of the amine group by hydrazinolysis followed by protecting the amine group with Boc. Finally, Separation of cis3b was the same as above.2. Synthesis of trans-3-(tert-butyloxycarbonyl)aminocyclohexanol.Trans3b was prepared by the conversion of cis-3-(tert-butyloxycarbonyl) aminocyclohexyltosylate with an excess of tetrabutylammonium p-nitrobenzoate in acetone followed by hydrolysis of the ester. Conversion of 3d by Mitsunobu reaction followed by hydrolysis of the ester gave trans-1,3-aminoalcohol. The substrate was released of the amine group by hydrazinolysis followed by protecting the amine group with Boc. Finally, Separation of trans3b was carried out by fractional crystallization with dichlromethane.