Читать книгу Routes to Essential Medicines - Peter J. Harrington - Страница 77

Antiparkinsonism Medicines

A tertiary alcohol is often formed by addition of an alkylmagnesium halide or arylmagnesium halide to a ketone (Grignard Reaction).

Discussion. Biperiden is a mixture of (exo,R,1S)‐ and (exo,S,1R)‐enantiomers. The retrosynthetic analysis of the (exo,R,1S)‐enantiomer is shown. The tertiary alcohol is formed from phenylmagnesium chloride and the ketone (Grignard Reaction). (How is biperiden separated from the mixture of stereoisomers that is formed in the Grignard Reaction?) Phenylmagnesium chloride is formed from chlorobenzene. The β‐piperidinoethyl ketone is formed by the reaction of the methyl ketone with formaldehyde and piperidine (Mannich Reaction). (Some exo‐to‐endo isomerization is observed in the Mannich Reaction. What reaction conditions are associated with the minimum amount of exo‐to‐endo isomerization?) A mixture of four stereoisomers of 2‐acetyl‐5‐norbornene is formed in the [4 + 2]‐cycloaddition of cyclopentadiene with methyl vinyl ketone (Diels–Alder Reaction). (Draw the structures of the stereoisomers.) The endo‐stereoisomers are isomerized to the exo‐stereoisomers.