Trimethyl borate → 1-N-Boc-pyrrolidin-2-ylboronic acid

Participants

Reaction Steps

N-acetyl-gly-boroproline 5 was prepared according to the synthetic route of FIG. 1. Metallation of tert-butyl 1-pyrrolidinecarboxylate (N-t-BOC-pyrrolidine, Sigma-Aldrich Co.) in THF with sec-butyllithium, followed by addition of trimethylborate gave 1-(tert-butoxycarbonyl)pyrrolidin-2-yl-2-boronic acid 1 after quenching with aqueous NaOH and extraction. Borate esterification with the (1S, 2S, 3R, 5S), (+)-pinanediol in methyl, tert-butyl ether (MTBE) gave borate ester 2. Acid hydrolysis of the BOC protecting group and selective crystallization in isopropyl alcohol gave (+)-pinane 1-pyrrolidin-2-yl-2-boronate 3. Coupling of 3 and N-acetyl glycine with EDC (N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide), HOBt (1-hydroxybenzotriazole), and DiPEA (diisopropylethylamine gave the pinane borate of N-acetyl-gly-boroproline 4. Borate exchange of 4 with phenylboronic acid in MTBE and water gave N-acetyl-gly-boroproline 5.

Provenance & Evidence