A stereospecific synthesis of the biologically active compound (+)-CP-99,994 was achieved. The key step in this process was a ring-expansion rearrangement, in which threo-fused monosubstituted prolinol was effectively transformed to 2,3-disubstituted piperidine with a cis-relationship, without loss of enantiomeric excess. Finally, D-proline methyl ester was successfully transformed to (+)-CP-99,994 in 10 steps (total yield of 23%).