4-Bromotoluene → Tolylboronic acid

Participants

Reaction Steps

p-Boronophenylalanine can be synthesized by the scheme illustrated in FIG. 5D. Accordingly, from p-bromotoluene 81 by Grignard reaction and treatment with triethylborate at -78° C. followed by hydrolysis gave p-boronotoluene 82. This on bromination and oxidation gave 84 according to Snyder et al. (1958) J Am Chem Soc 80:835-838. Further treatment with N-methyldiethanolamine in THF afforded the cyclic boronate, which on reaction with ethylisocyanate and sodium hydride at -70°-20° C. gave (Z)-ethyl α-formyl cinnamate derivative 86. Catalytic hydrogenation of 86 gave boronophenylalanine ethyl ester derivative 87. Finally, 87 was treated with sodium hydroxide and HCl in one pot to afford boronophenylalanine.

Provenance & Evidence