Process for the preparation of optionally substituted phenyl and pyridyl pyrrolidines

Process for the preparation of a compound of formula (X)

• wherein
• Z represents C—X3 or a nitrogen atom,
• X1, X2, X3, X4 and X5 independently of each other are selected from the group consisting of hydrogen, halogen, cyano, C1-C12-alkyl, C1-C12-haloalkyl, C1-C12-alkoxy and C1-C12-haloalkoxy;
• comprising
• step (i):
• reacting a compound of formula (II)
• in which
• X1, X2, X4, X5 and Z have the above mentioned meanings,
• with a compound of formula (III)
• T-CH2—S(O)mR (III)
• in which
• T is an anion stabilizing group;
• R is C1-12-alkyl, C1-6-haloalkyl, phenyl, or phenyl-C1-6-alkyl;
• m is 0, 1 or 2;
• optionally in the presence of a solvent, in the presence of a base and optionally in the presence of an additive, to obtain a compound of formula (IV),
• in which
• X1, X2, X4, X5, R, m and Z have the above mentioned meanings,
• step (ii):
• reacting a compound of formula (IV),
• (ii-a) with a compound of formula (V)
• in which
• R1 is selected from the group consisting of C1-12-alkyl, C1-6-haloalkyl, phenyl, and phenyl -C1-6-alkyl;
• R2, R3 and R4 independently of each other are selected from the group consisting of C1-12-alkyl, C1-6-haloalkyl, phenyl, and phenyl-C1-6-alkyl;
• Q is selected from the group consisting of aryl-C1-C6-alkyl, C1-C6-alkoxy-(C1-C6)-alkyl, C1-C6-alkyl-(O—CH2)n, and C2-C6-alkenyl;
• in the presence of an acid or a fluoride salt;
• or
• (ii-b) with a compound of formula (Va)
• in which
• Q has the above mentioned meanings,
• in the presence of formaldehyde or a formaldehyde equivalent, and in the presence of a solvent,
• in which process the water formed during the reaction is removed from reaction mixture,
• to obtain a compound of formula (VI)
• in which
• X1, X2, X4, X5, R, m, Q and Z have the above mentioned meanings,
• which is converted into a compound of formula (I)
• in which
• X1, X2, X4, X5, Q and Z have the above mentioned meanings,
• by (iii-a)
• heating a compound of formula (VI) in which m represents 1, optionally in the presence of a base, if appropriate in the presence of a solvent (iii-a-1),
• to obtain a compound of formula (VII)
• in which
• X1, X2, X4, X5, Q and Z have the above mentioned meanings,
• which is subjected to a catalytic hydrogenation, or to a reduction reaction using a hydride source in an appropriate solvent (iii-a-2) or,
• by (iii-b)
• removing the S(O)mR group by reacting a compound of formula (VI) in which m represents 2, with an elemental metal in the presence of a solvent, and optionally in the presence of a metal salt;
• or,
• by(iii-c)
• removing the S(O)mR group from a compound of formula (VI) in which m represents 0 or 1 by catalytic hydrogenation in the presence of a solvent and optionally a base optionally comprising triethylamine or sodium carbonate or an acid optionally comprising hydrochloric acid, acetic acid, and
• (iv)
• replacement of group Q by hydrogen to obtain a compound of formula (X),
• or
• reacting a compound of formula (IV) (ii-aa) with a compound of formula (V-1)
• in which
• R1, R2, R3 and R4 have the above mentioned meanings and
• Q1 is selected from the group consisting of C1-C6-alkyl-(O—CH2)n, or
• R1 and Q1 together with the atoms to which they are attached form a ring selected from
• wherein the dotted line is the bond to the carbon atom adjacent to the Si-atom in formula (V-1);
• in the presence of an acid or a fluoride salt
• to obtain a compound of formula (VIa)
• in which
• X1, X2, X4, X5, R, m and Z have the above mentioned meanings,
• which are converted into a compound of formula (X)
• by (iii-aa)
• heating a compound of formula (VIa) in which m represents 1, optionally in the presence of a base, if appropriate in the presence of a solvent (iii-aa-1),
• to obtain a compound of formula (VIIa)
• in which
• X1, X2, X4, X5 and Z have the above mentioned meanings,
• which is subjected to a catalytic hydrogenation, or to a reduction reaction using a hydride source in an appropriate solvent (iii-aa-2).