Process for preparing sodium salts or potassium salts of 4-hydroxy-2-oxo-2,5-dihydrofuran-3-carboxylate
View Patent ↗Process for preparing sodium or potassium salts of 4-hydroxy-2-oxo-2,5-dihydrofuran-3-carboxylic esters, comprising the reaction of a malonic ester with potassium hydroxide to give the corresponding malonic ester potassium salt of the formula (III) which is then reacted further with a chloroacetic ester to give a compound of the formula (V) followed by a ring closure reaction in which the compound of the formula (V) is reacted with a sodium or potassium alkoxide of the formula ZOR 1 where R 1 , R 2 , R 3 and K are each as defined in the description.
1. A process for preparing a sodium or potassium salt of 4-hydroxy-2-oxo-2,5-dihydrofuran-3-carboxylic ester of formula (I)
in which
Z is sodium or potassium, and
R 1 is C 1 -C 12 -alkyl,
comprising:
(i): reacting a symmetric malonic ester of formula (II)
with potassium hydroxide to give the corresponding malonic ester potassium salt of formula (III)
in which, in formulae (II) and (III),
R 2 is C 1 -C 12 -alkyl,
in a solvent;
(ii): reacting a malonic ester potassium salt of formula (III) with a chloroacetic ester of formula (IV)
in which
R 3 is C 1 -C 12 -alkyl,
to give a compound of formula (V)
in which
R 2 has the definitions listed in relation to formula (III), and
R 3 has the definitions listed in relation to formula (IV),
(iii): reacting a compound of formula (V) with a sodium or potassium alkoxide of formula ZOR 1 in which
R 1 is C 1 -C 12 -alkyl, and
Z is sodium or potassium,
wherein after addition of the chloroacetic ester in (ii), the reaction mixture is subjected to azeotropic dewatering,
in which, in (ii), from 0.8 to 5.0% by weight of water is added again to the reaction mixture after performance of the azeotropic dewatering,
and in which (ii) is performed in substance.
2. The process according to claim 1 , in which an aqueous potassium hydroxide solution is used in (i), and in which the solvent in (i) is an alcohol.
3. The process according to claim 1 , in which, on completion of conversion in (i), the malonic ester potassium salt of formula (III) is separated from unconverted malonic ester of formula (II) by phase separation before said malonic ester potassium salt is used in (ii).
4. The process according to claim 1 , in which, in (iii), sodium methoxide, sodium ethoxide, potassium methoxide or potassium ethoxide is used.
5. The process according to claim 4 , in which the sodium methoxide or the potassium methoxide is present dissolved in methanol, and the sodium ethoxide or the potassium ethoxide is present dissolved in ethanol.
6. The process according to claim 1 , wherein Z is sodium.
7. The process according to claim 1 , wherein Z is potassium.
8. The process according to claim 1 , wherein R2 is methyl.
9. The process according to claim 1 , wherein R2 is ethyl.
10. The process according claim 1 , wherein R3 is methyl or ethyl.
11. The process according to claim 3 , wherein the malonic ester potassium salt of formula (III) is used in step (ii) without further purification after the separation.
12. The process according to claim 1 , wherein the malonic ester potassium salt of formula (III) is not isolated in solid form at any time.
13. The process according to claim 1 , wherein dimethylformamide or dimethylacetamide are not used.