Synthesis of 7-(4-Trifluoromethyl)benzylidine-
3,3a,4,5,6,7-hexahydro-2,5-disubstituted-
3-(4-trifluoromethyl)phenyl-2H-pyrazolo[4,3-c]pyridines

The piperidone (1) was reacted with 2 equiv. of 4-trifluoromethylbenzaldehyde to produce 2 in high yield. Treatment of 2 with mono-substituted hydrazines provided 3. When the hydrazine substituent was either a bulky aliphatic group or an aryl group, we often obtained some 4 as a byproduct. For example, when NH₂NHCH(CH₃)₂ was reacted with 2 (R' = CH₂CH₂OCH₃), 3 and 4 were obtained in an 85:15 ratio.

When NH₂NHCH₂CF₃ was reacted with 2, however, the major product was 4. This posed a problem for the mixture synthesis (see Figure 1).