Process for the preparation of pyridinyl and pyrimidinyl mono-fluorinated beta keto-esters
View Patent ↗The present invention relates to a process for preparing pyridinyl and pyrimidinyl mono-fluorinated beta keto esters of formula (I): wherein: R1 represents a pyridine ring or a pyrimidine ring, the rings being optionally substituted by a C 3-6 cycloalkyl group, a C 1-4 alkyl group, a C 1-4 alkoxy group, a benzyl group or a halogen atom; R2 represents a hydrogen atom, a C 1-6 alkyl group or ahalogenatom; and R3 represents a C 1-6 alkyl group; by reacting with fluorine a compound of formula (II) wherein R1, R2 and R3 have the same meaning as defined above.
1. A process for the preparation of pyridinyl or pyrimidinyl mono-fluorinated beta keto esters of formula (I):
wherein:
R1 represents a pyridine ring or a pyrimidine ring, wherein the rings are optionally substituted by C 3-6 cycloalkyl, C 1-4 alkyl, C 1-4 alkoxy, benzyl or halogen;
R2 represents hydrogen, C 1-6 alkyl or halogen; and
R3 represents C 1-6 alkyl;
comprising:
reacting with fluorine gas a compound of formula (II) in the presence of one or more acids,
wherein R1, R2 and R3 have the same meaning as defined above.
2. The process according to claim 1 , wherein the acid is chosen from formic acid, trifluoroacetic acid, sulfuric acid, trifluoromethanesulfonic acid and hydrofluoric acid.
3. The process according to claim 2 , wherein the reaction is carried out in the absence of solvent.
4. The process according to claim 2 , wherein the reaction is carried out in the presence of an inert solvent, wherein said solvent is acetonitrile or chloroform.
5. The process according to claim 3 , wherein the reaction is carried out in the presence of hydrofluoric acid in absence of solvent.
6. The process according to claim 1 , wherein:
R1 represents a 3 or 4-pyridinyl or a 4- or 5-pyrimidinyl, optionally substituted by a C 1-2 alkyl group, and
R2 represents hydrogen or C 1-3 alkyl; and
R3 represents C 1-3 alkyl.
7. The process according to claim 1 , wherein the compound of formula (I) is:
ethyl 2-fluoro-3-oxo-3-pyridin-4-yl propanoate or ethyl 2-fluoro-3-oxo-3-pyrimidin-4-yl propanoate.
8. A compound of formula (I):
wherein
R1 represents a pyridine ring or a pyrimidine ring, wherein the rings are optionally substituted by C 3-6 cycloalkyl, C 1-4 alkyl, C 1-4 alkoxy, benzyl or halogen;
R2 represents hydrogen, C1–6 alkyl or halogen; and
R3 represents C1–6 alkyl; with the proviso that compound of formula (I) is not ethyl 2-fluoro-3-oxo-3-pyridin-4-yl propanoate.
9. The compound according to claim 8 which is ethyl 2-fluoro-3-oxo-3-pyrimidin-4-yl propanoate.
10. The compound according to claim 8 wherein R1 is an optionally substituted pyrimidine ring.