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 process for the preparation of a compound having the formula:
which comprises reacting 2-(thien-2-yl)ethylamine having the formula
in the form of a base or a salt, with an (R)-sulphonyloxyacetic ester having the formula
wherein R 1 is benzyl, C 1 –C 4 -alkyl optionally substituted by one or more halogens, or phenyl optionally substituted by nitro, one or more halogens or one or more C 1 –C 4 -alkyl groups, in the presence of a base, used alone or in aqueous solution and reacting the resulting compound of the formula
with a formylation agent, and effecting cyclization in the presence of an acid to give the desired compound.
2. A process according to claim 1 wherein the formylation agent is chosen from formaldehyde, its hydrate or its polymerisation derivatives, compounds with the general formula:
R 3 —CH 2 —R 4
in which R 3 represents a halogen atom, a C 1 –C 4 alkoxy group, a C 1 –C 4 alkylthio group or an amino group and R 4 represents a C 1 –C 4 alkoxy group, a C 1 –C 4 alkylthio group, a C 2 –C 5 alkoxycarbonyl or phenoxycarbonyl group or heterocyclic compounds with the general formula:
in which Z represents O, NH, or S.
3. A process according to claim 2 wherein the formylation agent is chosen from formaldehyde, its hydrate or its polymerisation derivatives.
4. A process according to claim 1 wherein the reaction with the (R)-sulphonyloxyacetic ester takes place in a polar or non-polar solvent.
5. A process according to claim 1 wherein the reaction with the formylation agent and the cyclisation take place simultaneously in a polar solvent.
6. A process according to claim 5 wherein the acid is formic acid, which is also used as the solvent.
7. A process according to claim 1 wherein R 1 is phenyl, 4-chlorophenyl, 4-nitrophenyl or 2,5-dichlorophenyl.
8. A process according to claim 1 wherein formylation and cyclization take place successively.
9. A process for the preparation of a compound having the formula
which comprises reacting a compound having the formula
with a formylation agent and cyclizing the resulting product.
10. A process according to claim 9 wherein the formylation agent is formaldehyde.
11. A process according to claim 10 wherein cyclization takes place in the presence of hydrochloric acid.