Synthetic process for preparing 2-furoic acid derivatives
View Patent ↗Disclosed herein are processes for forming 2-furoic acid derivatives represented by Formula (I):
1. A process for preparing a compound of Formula (I)
comprising:
converting a compound of Formula (II) to an intermediate compound of Formula (III):
and
saponifying the intermediate compound of Formula (III) to form the compound of Formula (I),
wherein,
R 1 is alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl;
R 2 is C 1-4 alkyl; and
X is halo;
wherein converting the compound of Formula (II) to the intermediate of Formula (III) comprises:
transesterifying the compound of Formula (II) with R 1 —OH to form an intermediate compound of Formula (IV)
and
converting the intermediate compound of Formula (IV) to the intermediate compound of Formula (III) in the presence of R 1 —OH and a base.
2. The process of claim 1 wherein R 1 is C 10-20 alkyl.
3. The process of claim 2 wherein R 1 is —C 14 H 29 .
4. The process of claim 1 wherein R 2 is methyl.
5. The process of claim 1 wherein X is Br or Cl.
6. The process of claim 1 wherein the base is characterized with having a conjugate acid having a pKa of at least 15.
7. The process of claim 1 further comprising removing R 2 —OH produced during transesterifying of the compound of Formula (II).
8. The process of claim 7 wherein the removal is carried out in the presence of a Lewis acid.
9. The process of claim 8 wherein the Lewis acid is titanium tetraisopropoxide.
10. The process of claim 1 wherein transesterifying of the compound of Formula (II) is carried out at a temperature below 120° C.
11. The process of claim 1 wherein converting the intermediate compound of Formula (IV) to the intermediate compound of Formula (III) is carried out at a temperature below 60° C.
12. The process of claim 1 wherein saponifying the intermediate compound of Formula (III) is carried out in the presence of a base at a temperature below 50° C.
13. The process of claim 12 wherein the base is a metal hydroxide combined with an alcohol.
14. The process of claim 13 wherein base is potassium hydroxide combined with methanol.
15. The process of claim 1 wherein the compound of Formula (I) is 5-tetradecyloxy-2-furoic acid.