Methods for the preparation of 1,3-benzodioxole heterocyclic compounds

1. A method for the preparation of a compound of formula (I)

wherein R 1 is selected from CHF 2 and CF 3 , Q is selected from chloro, bromo and fluoro, comprising each of the steps:

(1) reacting a compound of formula (II)

wherein R 2 is selected from hydrogen, C 1-6 -alkyl and arylalkyl, R 21 is C(O)CH 3 ; with a compound of formula (III)

wherein “ ” represents a single bond, a double bond or two single bonds, and when “ ” represents a double bond or two single bonds, “==” is a single bond, and when “ ” represents a single bond, “==” is a double bond, R 3 represents oxygen when “ ” represents a double bond and R 3 represents O—C 1-6 -alkyl when “ ” represents a single bond or two single bonds

in the presence of an acid catalyst to form a compound of formula (IV)

wherein R 2 and R 21 are as defined above;

(2a) reacting the resulting compound of formula (IV) with a pyridine compound of formula (V)

wherein Q is as defined above and Q X is selected from chloro, bromo, fluoro and iodo to form an intermediate compound of formula (VI)

wherein R 2 and Q are as defined above;

(2b) reacting the compound of formula (VI) wherein R 2 is selected from C 1-6 -alkyl and arylakyl with a compound of formula (VII)

wherein R 4 and R 5 represent C 1-6 -alkyl, to form a compound of formula (VIII)

wherein Q is defined above;

(2c) reacting the compound of formula (VIII) with aqueous N(Bu 4 ) + OH − to form a compound of formula (IX)

wherein Q is as defined above; followed by alkylating and subsequent oxidation of the resulting compound to prepare the compound of formula (I) wherein R1and Q are as defined above.

2. The method according to claim 1 wherein in step (1), the acid catalyst is in form of the silicate mineral Montmorillonite K10.

3. The method according to claim 1 wherein in step (2a) is conducted in an aprotic polar solvent in the presence of a base.

4. The method according to claim 1 wherein step (2b) is conducted in a solvent selected from NMP, DMSO, DMF and mixtures thereof, in the presence of a base.

5. The method according to claim 1 wherein R 1 is CHF 2 .

6. The method according to claim 1 wherein all of Q and Q x are chloro.

7. The method according to claim 1 , wherein the alkylating and subsequent oxidation steps comprise alkylating the compound of formula (IX) by reacting with a hydrochlorofluorocarbon compound, R 1 -CI, wherein R 1 is as defined in claim 1 , to form a compound of formula (XI)

wherein R 1 and Q are as defined in claim 1 ; and oxidation of the compound of formula (XI) to prepare the compound of formula (I) wherein R 1 and Q are as defined in claim 1 .

8. The method according to claim 7 wherein alkylating the compound of formula (IX) is conducted using a hydrochlorofluorocarbon in the presence of an aprotic polar solvent.

9. The method according to claim 7 wherein the oxidation of the compound of formula (XI) is conducted using peracetic acid in acetic acid.