Stereoselective one step fluorination process for the preparation of 2-flouropropionate
View Patent ↗The current invention describes a one-step process for the synthesis of 2-fluoropropionates from lactic acid ester derivatives using TFEDMA.
1. Process for the production of a compound of the formula (II)
wherein
** marks an asymmetric carbon atom,
R 1 is optionally substituted C 1 -C 4 alkyl and
R 2 is methyl which is optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, nitro, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, (C 1 -C 4 -alkoxy)carbonyl, C 1 -C 4 -alkylamino, di-(C 1 -C 4 -alkyl)amino, C 3 -C 6 -cycloalkylamino and (C 1 -C 4 -alkyl) C 3 -C 6 -cycloalkylamino,
characterized in that tetrafluoroethyldimethylamine is reacted with a lactic acid derivative of the formula (I)
wherein
* marks an asymmetric carbon atom in R- or S-configuration and
R 1 and R 2 have the meaning given above,
the carbon atom marked ** in formula (II) having inversed configuration in comparison the corresponding carbon atom marked * in formula (I).
2. Process according to claim 1 characterized in that the reaction takes place in the presence of an inert diluent.
3. Process according to claim 1 characterized in that between 0.75 and 3 moles of tetrafluoroethyldimethylamine are reacted per mole of lactic acid derivative of formula (I).
4. Process according to claim 1 , characterized in that R 1 and R 2 each represent methyl.
5. Process according to claim 1 characterized in that the compound of formula (II) is (R)-methyl-2-fluoroproprionate and the lactic acid derivative of the formula (I) is (S)-methyl lactate.
6. Process according to claim 1 , characterized in that the compound of formula (II) is (S)-methyl-2-fluoroproprionate and the lactic acid derivative of the formula (I) is (R)-methyl lactate.
7. Process according to claim 1 , wherein R 1 is methyl, ethyl, n-propyl or i-propyl.
8. Process according to claim 1 , wherein R 2 is methyl or ethyl both optionally substituted by one or more substituents selected from the group consisting of chlorine, bromine, iodine and fluorine.
9. Process according to claim 1 , wherein R 1 is methyl or ethyl.
10. Process according to claim 1 , wherein the compound of formula (II) has an ee of >95% relative to its inverse configuration.