4-methyl hydrogen D-aspartate hydrochloride

Uses

D-Aspartic acid 4-methyl ester is a protected form of D-Aspartic acid (A790020). D-Aspartic acid is the unnatural isomer of L-Aspartic acid (A790024). D-Aspartic acid naturally occurs in human ovarian follicular fluid, and is thought to be linked to oocyte quality. It is also found in the white matter of human brains, more specifically in myelin proteins.

Synthesis

The general procedure for the synthesis of (R)-2-amino-4-methoxy-4-oxobutanoic acid hydrochloride from methanol and D-aspartic acid was as follows: D-aspartic acid (160 g, 1.2 mol) was suspended in 850 mL of methanol and cooled to -5 to 0°C. Thionyl chloride (178.4 g, 1.5 mol) was added slowly dropwise with stirring. After completion of the dropwise addition, the reaction mixture was slowly warmed to 25 to 35°C and the reaction was continued with stirring for 4 to 5 hours. Upon completion of the reaction, the methanol was removed by distillation under reduced pressure. The resulting white solid was washed with stirring in 500 mL of ethyl acetate for 0.5 h. Subsequent filtration and drying afforded the target product (R)-2-amino-4-methoxy-4-oxobutanoic acid hydrochloride (Compound of Formula II) 192 g in 87% yield with a melting point of 185 to 186°C. The reaction mixture was slowly warmed to 25 to 35°C for 4 to 5 hours.

References

[1] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 17, p. 2513 - 2526
[2] Patent: CN103992337, 2016, B. Location in patent: Paragraph 0031; 0032
[3] Patent: CN104497010, 2016, B. Location in patent: Paragraph 0035; 0036; 0037
[4] Journal of Medicinal Chemistry, 1994, vol. 37, # 5, p. 674 - 688