Process for the production of 2(2-aminophenyl)-bicylopropane derivatives
View Patent ↗The present invention relates to a process for the preparation of compounds of formula (I) wherein the substituents are as defined in claim 1 , by a) reaction of a compound of formula (II) to form a compound of formula (III) b) reaction of that compound in the presence of a base to form a compound of formula (IV) c) conversion of that compound in the presence of a reducing agent into a compound of formula (I).
1. A process for the preparation of a compound of formula I
wherein R 1 , R 2 and R 3 are each independently of the others hydrogen or methyl, which comprises
a) reaction of a compound of formula II
wherein R 1 , R 2 and R 3 are as defined for formula I, either
a1) with triphenylphosphine dibromide or triphenylphosphine dichloride or
a2) with RSO 2 Cl, wherein R is C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl, benzyl, phenyl, nitrophenyl, halophenyl or C 1 -C 6 alkylphenyl, in the presence of a base,
to form a compound of formula III
wherein X is OSO 2 R, wherein R is C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl, benzyl, phenyl, nitrophenyl, halophenyl or C 1 -C 6 alkylphenyl, or is bromine or chlorine and R 1 , R 2 and R 3 are as defined for formula I; and
b) reaction of that compound in the presence of a base to form a compound of formula IV
wherein R 1 , R 2 and R 3 are as defined for formula 1; and
c) conversion of that compound in the presence of a reducing agent into a compound of formula I.
2. A process according to claim 1 , which comprises, after carrying out Process Step b) and before carrying out Process Step c), isomerisation of the compound of formula IV
wherein R 1 , R 2 and R 3 are as defined for formula I in claim 1 ,
bb) in the presence of a base to form a compound of formula IV wherein the ratio of the compound of formula IVa (trans)
wherein R 1 , R 2 and R 3 are as defined for formula I in claim 1 , to the compound of formula IVb (cis)
wherein R 1 , R 2 and R 3 are as defined for formula I in claim 1 , is more than 6:1.
3. A compound of formula III
wherein R 1 , R 2 and R 3 are each independently of the others hydrogen or methyl and X is OSO 2 R, wherein R is C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl, benzyl, phenyl, nitrophenyl, halophenyl or C 1 -C 6 alkylphenyl, or is bromide or chlorine.