Hydroxyacetic ester derivatives, preparation method and use as synthesis intermediates
View Patent ↗Methyl (R)-2-(R 1 OSO 2 )-2-(2-chlorophenyl)acetates useful as intermediates in the preparation of methyl (S)-2(2-chlorophenyl)-2-(4,5,6,7-tetrahydrothieno[3,2-c]-5-pyridyl)acetate.
1. A compound of the formula:
in which R1 represents a benzyl group, a C 1 -C 4 alkyl, which may be substituted by one or several halogen atoms or a phenyl group, which may be substituted by one or several halogen atoms or by one or several linear or branched C 1 -C 4 alkyl groups or by a nitro group.
2. A compound according to claim 1 , in which R 1 represents a methyl, ethyl, propyl, trifluoromethyl, benzyl, phenyl, chlorophenyl, dichlorophenyl, tolyl, trimethylphenyl, triisopropylphenyl, or nitrophenyl group.
3. Methyl(R)-2-benzenesulphonyloxy-2(2-chlorophenyl) acetate according to claim 2 .
4. Methyl(R)-2(2-chlorophenyl)-2(2,4,6-trimethylbenzenesulphonyloxy) acetate according to claim 2 .
5. Methyl(R)-2(4-chlorobenzenesulphonyloxyl)-2(2-chlorophenyl) acetate according to claim 2 .
6. Methyl(R)-2(2-chlorophenyl)-2(4-nitrobenzenesulphonyloxy) acetate according to claim 2 .
7. Methyl(R)-2(2-chlorophenyl)-2(2,4,6-triisopropylbenzene-sulphonyloxy) acetate according to claim 2 .
8. Methyl(R)-2(2-chlorophenyl)-2(2,5-dichlorobenzenesulphonyloxy) acetate according to claim 2 .
9. A process for the preparation of a compound according to claim 1 which comprises reacting a (R)-2(2-chlorophenyl)-2-hydroxy acetic ester of the formula:
with a sulphonyl anhydride or halogenide with the formula:
R 1 —SO 2 —R 2 III
in which R 2 represents an OSO 2 —R 1 group or a halogen atom and R 1 has the same significance as in claim 1 , the reaction taking place in the presence of a lithium salt and an aromatic amine to form the desired compound of formula I.
10. A process according to claim 9 wherein the lithium salt used is lithium perchlorate or lithium tetrafluoroborate.
11. A process according to claim 9 wherein the lithium salt is used in a quantity of 1 or 1.2 molar equivalent per molar equivalent of the formula III-compound.
12. A process according to claim 9 wherein the aromatic amine used is pyridine or 4-dimethylaminopyridine.
13. A process according to claim 12 wherein the aromatic amine is used in a quantity of 1 to 1.2 molar equivalent per molar equivalent of the formula-III compound.
14. A process according to claim 9 wherein the reaction takes place at a temperature of between 0° C. and room temperature.
15. A process for the preparation of a compound according to claim 1 which comprises reacting a (R)-2(2-chlorophenyl)-2-hydroxy acetic ester of the formula:
with a sulphonyl anhydride or halogenide, with the formula
R 1 —SO 2 —R 2 III
in which R 2 represents an OSO 2 —R 1 group or a halogen atom and R 1 has the same significance as in claim 1 , the reaction taking place in the presence of 4-dimethylaminopyridine and another acid acceptor, to yield the desired compound of Formula I.
16. A process according to claim 15 wherein the acid acceptor is an amine.
17. A process according to claim 15 wherein the reaction takes place at a temperature of between −10° C. and +10° C.
18. A process according to claim 9 wherein the reaction takes place in an aprotic solvent.
19. A process according to claim 18 wherein the aprotic solvent is a halogenated hydrocarbon.
20. A process according to claim 15 wherein the reaction takes place in an aprotic solvent.
21. A process according to claim 20 wherein the aprotic solvent is a halogenated hydrocarbon.