Uses
3-(2-Amino-2-oxoethyl)-5-methylhexanoic Acid is a Pregabalin, a GABA analogue used as an anticonvulsant, intermediate.
Uses
3-(2-Amino-2-oxoethyl)-5-methylhexanoic Acid is a Pregabalin (P704800), a GABA analogue used as an anticonvulsant, intermediate.
Synthesis
The general procedure for the synthesis of 3-(aminocarbonylmethyl)-5-methylhexanoic acid using 4-isobutyldihydro-2H-pyran-2,6(3H)-dione as a starting material was as follows: first, 70 g of the dried product of 3-isobutylglutaric acid was reacted with 70 g of acetic anhydride at 120 °C for 2 h to produce 3-isobutylglutaric anhydride. Subsequently, 75g of 3-isobutylglutaric anhydride solution was slowly added dropwise to 180g of ammonia, and the temperature was controlled at 10°C during the reaction. After the dropwise addition, the reaction was continued for 2 hours. After the completion of the reaction, the pH of the solution was adjusted to 2~3 with hydrochloric acid, and a white powdery solid was obtained by filtration, i.e., the target product 3-isobutylglutaric acid monoamide. Liquid phase detection of the product showed a purity of 99.8%, a yield of 95% and an overall yield of 77.5%. Figure 4 illustrates the liquid phase assay results of 3-isobutylglutaric acid monoamide.
References
[1] Patent: CN106278931, 2017, A. Location in patent: Paragraph 0038; 0039; 0040
[2] Patent: WO2012/93411, 2012, A2. Location in patent: Page/Page column 18-19
[3] Patent: WO2009/4643, 2009, A2. Location in patent: Page/Page column 26
[4] Organic Process Research and Development, 2009, vol. 13, # 4, p. 812 - 814
