Method for the production of fluoromethyl-substituted heterocycles

1. A process for preparing fluoromethyl-substituted heterocycles of formula (I)

in which

R 1 is, fluorine or chlorine,

R 2 is hydrogen,

R 3 is C 1 -C 6 -alkyl,

A is a pyrazole that is substituted by R 4 in the 1-position, and

R 4 is C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkylthio-C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, or phenyl,

comprising converting a chloromethyl-substituted heterocycle of formula (II)

in which

R 1 is chlorine, and

R 2 , R 3 , and A are each as defined for formula (I), to a fluoromethyl-substituted heterocycle of formula (I) in the presence of a fluorinating agent selected from the group consisting of 3 HF/N(Et) 3 (Franz reagent), 3 HF/N(n-Bu) 3 , and HF/pyridine (Olah's reagent) and optionally in the presence of a diluent.

2. A process according to claim 1 wherein for the chloromethyl-substituted heterocycle of formula (II),

R 1 is chlorine,

R 2 is hydrogen,

R 3 is C 1 -C 4 -alkyl,

A is a pyrazole selected from the group consisting of

 where in each case the bond marked by * is joined to the —CClR 1 R 2 group and the other bond is joined to the CO 2 R 3 ester group, and

R 4 is methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclopentyl, cyclohexyl, or phenyl.

3. A process according to claim 1 wherein the chloromethyl-substituted heterocycle of formula (II) is selected from the group consisting of compounds of formulas (II-a), and (II-b)

in which R 1 , R 2 , and R 3 are as defined for formula (II) in claim 1 .

4. A process according to claim 3 in which R 3 is methyl or ethyl.

5. A process according to claim 1 wherein the fluorinating agent is 3 HF/N(Et) 3 (Franz reagent) or 3 HF/N(n-Bu) 3 .

6. A process according to claim 1 that is carried out at a temperature of 80° C. to 170° C.

7. A process according to claim 1 that is carried out at a temperature of 120° C. to 150° C.