Precursor compounds for the radiosynthesis of [18F] norchloro-fluorohomoepibatidine

A method for the preparation of a compound of formula Ia

• wherein:
• R4 represents —CO2R3, —COR4 or —R5, wherein
• R3 represents unsubstituted or substituted C1-C6 alkyl,
• R4 represents hydrogen, unsubstituted or substituted C1-C6 alkyl, and
• R5 represents hydrogen, unsubstituted or substituted C1-C6 alkyl,
• R2 represents —N+(R6)(R7)(R8)X− or nitro, wherein
• R6, R7, R8 independently of each other represent unsubstituted or substituted C1-C6 alkyl or unsubstituted or substituted —(CH2)n— with n=1 to 12 provided that at least two of the substituents R6, R7, and R8 are C1-C6 alkyl, and
• X− represents a halide, sulphonate, unsubstituted or substituted acetate, sulphate, hydrogen sulphate, nitrate, perchlorate, or oxalate.
• wherein the method comprises:
• the reaction of a compound of formula II with 2-fluoro-5-iodopyridine using a palladium catalyst
• to a compound of formula III
• the cleavage of the protective group in a compound of formula III with hydrogen using a palladium catalyst to obtain a compound of formula (IV)
• an enantiomeric separation of the compound of formula IV to obtain compounds of formula V and/or of formula VI
• and the substitution of the fluorine in a compound of formula V with a dialkylamine to obtain a compound of formula VII
• wherein R13 and R14 are independently selected from the group consisting of methyl, ethyl, and tert-butyl, the introduction of a protective group into the compound of formula VII to obtain a compound of formula VIII
• and the quaternization of the compound of formula VIII with an alkylating agent to a compound of formula Ia.