Process for reducing 3-heteroaryl-3-oxopropionic acid derivatives

1. A process for preparing ethyl 3-hydroxy-3-(2-thiophenyl) -propanoate from ethyl 3-oxo-3-(2-thiophenyl)-propanoate; methyl 3-hydroxy-3-(2-thiophenyl)-propanoate from methyl 3-oxo-3-(2-thiophenyl)-propanoate;

methyl 3-(3-chloro-l-benzothien-2-yl)-3-hydroxypropanoate from methyl 3-(3-chloro-1-benzothien-2-yl)-3-oxo-propanoate; methyl 3-hydroxy-3-(3-furanyl) -propanoate from methyl 3-oxo-3-(3-furanyl)-propanoate; or methyl 3-hydroxy-3-(2-furanyl)-propanoate from methyl 3-oxo-3-(2-furanyl)-propanoate; said process comprising reacting formic acid, formate or a mixture thereof with said ethyl 3-oxo-3-(2-thiophenyl)-propanoate; said methyl 3-oxo-3-(2-thiophenyl)-propanoate;

said methyl 3-(3-chloro-l-benzothien-2-yl)-3-oxo-propanoate; said methyl 3-oxo -3-(3-furanyl)-propanoate; or said methyl 3-oxo-3-(2-furanyl)-propanoate, wherein in each case said reacting is conducted in the presence of a ruthenium-containing catalyst and in the presence of at least one amine, at least some of which amine is present in protonated form.

2. Process according to claim 1 , which comprises preparing methyl 3-hydroxy -3-(2-thiophenyl)-propanoate from methyl 3-oxo-3-(2-thiophenyl)-propanoate.

3. Process according to claim 1 , wherein the ruthenium-containing catalyst used is a catalyst which comprises a ruthenium complex.

4. Process according to claim 3 , wherein the ruthenium complex is one of the formula (IV) or one obtainable by reacting a compound of the formula (II) with a compound of the formula (III) where, in the compound of the formula (II):

[RuX 2 (arene)] 2   (II),

arene is a coordinated aromatic compound having 6 to 12 ring carbon atoms which is optionally substituted by up to 6 radicals, each of which is independently selected from the group consisting of C 1 -C 8 -alkyl, benzyl and phenyl, and

X is chlorine, bromine or iodine,

and where, in the formula (III):

R 3 and R 4 are each independently C i -C 20 -alkyl, C 4 -C 15 -aryl or C 5 -C 16 -arylalkyl, or R 3 and R 4 together are a straight-chain or branched C 3 -C 12 -alkylene radical, and

R 5 is C 1 -C 20 -alkyl, C 1 -C 20 -fluoroalkyl or C 4 -C 15 -aryl,

and where, in the formula (IV):

[RuX 2 (arene){(III)}]  (IV),

arene and X are each as defined under formula (II) and (III) in the formula (IV) represents a compound of the formula (III) as defined there.

5. Process according to claim 4 , wherein the ruthenium complex used is one obtainable by reacting a compound of the formula (II) with a compound of the formula (III).

6. Process according to claim 5 , wherein the ruthenium complex used is one obtainable by reacting a compound of the formula (II) with a compound of the formula (III), wherein the molar ratio of the compound of the formula (III) to the compound of the formula (II) is 2:1 to 3:1.

7. Process according to claim 4 , wherein the compound of the formula (II) is the (benzene)dichlororuthenium dimer, the (mesitylene)dichlororuthenium dimer or the (cumene)dichlororuthenium dimer.

8. Process according to claim 4 , wherein the compound of the formula (III) is one wherein:

R 3 and R 4 are identical and are each phenyl or together are straight-chain C 3 -C 8 -alkylene, and

R 5 is C i -C 4 -alkyl, C i -C 4 -fluoroalkyl, phenyl or naphthyl which is substituted by none, one, two, three, four or five radicals which are selected from the group consisting of C i -C 4 -alkyl, C i -C 4 -alkoxy, C i -C 4 -fluoroalkyl, fluorine and chlorine.

9. Process according to claim 4 , wherein the compound of the formula (III) used is S,S- or R,R-N-p-toluenesulphonyl-1,2-diphenylethylenediamine.

10. Process according to claim 1 , wherein the amine, at least some of which is present in protonated form, is one of the formula (V):

NR 6 R 7 R 8   (V)

where

R 6 , R 7 and R 8 are each independently hydrogen, C i -C 8 -alkyl or benzyl.

11. Process according to claim 10 , wherein the amine, of which at least some is present in protonated form, is one of the formula (V) where R 6 , R 7 and R 8 are each independently C i -C 8 -alkyl or benzyl.

12. Process according to claim 1 , wherein a mixture of formic acid and triethylamine is used.

13. Process according to claim 1 , wherein the molar ratio of formic acid to amine is 1:1 to 3:1.

14. Process according to claim 1 , wherein the molar ratio of formic acid based on substrate used is 1:1 to 3:1.

15. Process according to claim 1 , which is carried out at a reaction temperature of -10 to 150° C.

16. Process according to claim 1 , which is carried out at a molar amount of ruthenium of 0.01 to 1.0 mol%, based on the substrate used.

17. Process according to claim 1 , which further comprises stirring a reaction mixture at an average stirrer speed of 100 to 3 000 min -1 .

18. Process according to claim 1 , which further comprises passing an inert gas stream through or over the reaction mixture.