Method for the preparation of n-monofluoroalkyl tropanes and their use

A method for the preparation of an N-monofluoroalkyl tropane of formula (VI)

• wherein n is 2, 3 or 4,
• comprising the steps:
• a) providing a compound of formula (I)
• b) reducing the carbonyl group to a hydroxyl group to give the compound of formula (II)
• c) performing a dehydration reaction to give the compound of formula (III)
• d) performing addition of a 4-bromophenyl moiety to give the compound of formula (IV)
• e) performing N-demethylation to give the compound of formula (V)
• f) performing alkylation with an alkylation agent of formula F—(CH2)n—Br in the presence of a base to give the N-monofluoroalkyl tropane of formula (VI), wherein n is 2, 3 or 4,
• the method comprising one chiral resolution, wherein the chiral resolution is performed after the alkylation in step f), to separate enantiomers and provide the N-monofluoroalkyl tropane of formula (VI).