Z-Phg-OH

Chemical Properties

White to off-white powder

Uses

Z-L-Phenylglycine is an intermediate for the synthesis of Asimadoline Hydrochlorine (A788250), used in the treatment of IBS, a disorder associated with pain and altered bowel function.

reaction suitability

reaction type: solution phase peptide synthesis

Synthesis

General procedure for the synthesis of the compound (CAS:5491-18-9) from L-phenylglycine and benzyl chloroformate: To an aqueous solution (500 mL) containing 2-amino-2-phenylacetic acid (20 g, 0.12 mol), sodium carbonate (27.97 g, 0.264 mol) and sodium bicarbonate (11.1 g, 0.132 mol) were added at room temperature. The mixture was stirred until a clarified solution was formed. Acetone (40 mL) was then added and the resulting slightly turbid solution was cooled to 15-20 °C in an ice water bath. Benzyl chloroformate (Cbz-Cl, 28.15 g, 0.165 mol) was added slowly with stirring and then the reaction mixture was gradually warmed to room temperature. After continued stirring for 3 h, the reaction mixture was extracted with methyl tert-butyl ether (100 mL). The pH of the aqueous layer was adjusted with aqueous hydrochloric acid to 2. The oil formed was extracted with ethyl acetate (100 mL x 2). The organic layers were combined, washed with water and concentrated under vacuum to give (S)-2-(((benzyloxy)carbonyl)amino)-2-phenylacetic acid (30.2 g, 80% yield) as a white solid.

References

[1] Tetrahedron Letters, 2006, vol. 47, # 36, p. 6393 - 6396
[2] Patent: WO2018/136647, 2018, A2. Location in patent: Page/Page column 29-30
[3] Tetrahedron Letters, 1993, vol. 34, # 39, p. 6329 - 6332
[4] Patent: WO2014/210436, 2014, A2. Location in patent: Paragraph 00520; 00521
[5] Patent: EP1076563, 2005, B1. Location in patent: Page/Page column 9; 13