Process for synthesizing trifluoroketones

1. A process for synthesizing trifluoroketone(s), the process comprising the steps of:

(a) a Suzuki coupling between a mixture of methyl- and/or ethyl-esters of 4-chloro-2-iodobenzoic acid and phenylboronic acid to form methyl- and/or ethyl-esters of 4-chloro-2-phenylbenzoic acid; and

(b) a catalyzed trifluoromethylation of the methyl- and/or ethyl-esters of the 4-chloro-2-phenylbenzoic acid of step (a) to form the corresponding trifluoroketone(s).

2. The process of claim 1 , wherein the trifluoroketone(s) formed in step (b) comprise 1-(5-chloro[1,1-biphenyl]-2-yl)-2,2,2-trifluoroethanone, 2,2,2-trifluoro-1-(2-bromo-4-chlorophenyl)ethanone, or 2,2,2-trifluoro-1-(4-chloro-2-iodophenyl)ethanone.

3. The process of claim 2 , wherein the phenylboronic acid of step (a) comprises phenylboronic acid having an unsubstituted phenyl group and wherein the trifluoroketone formed in step (b) comprises 1-(5-chloro[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroethanone.

4. The process of claim 1 , wherein step (a) is carried out at a temperature in the range of from about 55° to about 100° C.

5. The process of claim 4 , wherein step (a) is carried out at a temperature in the range of from about 75° to about 98° C.

6. The process of claim 1 , wherein the mixture of step (a) comprises a weight ratio of the methyl- and/or ethyl-esters of 4-chloro-2-iodobenzoic acid to the phenylboronic acid in the range of from about 1:1 to about 5:1.

7. The process of claim 6 , wherein the mixture of step (a) comprises a weight ratio of the methyl- and/or ethyl-esters of 4-chloro-2-iodobenzoic acid to the phenylboronic acid in the range of from about 1.1:1 to about 1.5:1.

8. The process of claim 1 , wherein the Suzuki coupling of step (a) is carried oat with a palladium complex catalyst.

9. The process of claim 8 , wherein palladium complex catalyst comprises palladium (0) tetrakis(triphenylphosphine) (Pd(PPh 3 ) 4 ).

10. The process of claim 7 , wherein the amount of palladium (0) tetrakis(triphenylphosphine)(Pd(PPh 3 ) 4 )) is in in the range of from about 0.0001 to about 100 mol %.

11. The process of claim 10 , wherein the amount of palladium (0) tetrakis(triphenylphosphine)(Pd(PPh 3 ) 4 )) is in in the range of from about 0.002 to about 0.01 mol %.

12. The process of claim 1 , wherein the methyl- and/or ethyl-esters of 4-chloro-2-iodobenzoic acid of step (a) comprise a mixture of methyl and ethyl esters of 4-chloro-2-iodobenzoic acid in a weight ratio of methyl esters to ethyl esters of from about 4:1:to about 15:1.

13. The process of claim 12 , wherein the weight ratio of methyl esters to ethyl esters is from about 7:1:to about 12:1.

14. The process of claim 1 , wherein the trifluoromethylation of step (b) is carried out by using trifluoromethyltrimethylsilane.

15. The process of claim 14 , wherein the trifluoromethylation of step (b) is carried out by using a weight ratio of methyl- and/or ethyl-esters of 4-chloro-2-phenylbenzoic acid to trifluoromethyltrimethylsilane of from about 1:1 to about 1.5:1.

16. The process of claim 15 , wherein the trifluoromethylation of step (b) is carried out by using a weight ratio of methyl- and/or ethyl-esters of 4-chloro-2-phenylbenzoic acid to trifluoromethyltrimethylsilane of form about 1.1:1 to about 1.3.

17. The process of claim 14 , wherein the trifluoromethylation of step (b) is carried out at a temperature in the range of from about −20° to about 60° C.

18. The process of claim 17 , wherein the trifluoromethylation of step (b) is carded out at a temperature in the range of from about 0° to about 20° C.

19. The process of claim 18 , wherein the trifluoromethylation of step (b) is carried out with cesium fluoride as the catalyst in an amount of from about 8 to about 20 weight %.

20. The process of claim 19 , wherein the cesium fluoride is used in an amount of from about 9.2 to about 10.2 weight %.

21. The process of claim 19 , wherein the trifluoromethylation of step (b) is carried out by using anhydrous tetrahydrofuran as the solvent.