Patent ID: 7714159

Claim:
A large-scale process for preparing a boronic ester compound of formula (I): wherein: R 1 is an optionally substituted aliphatic or aromatic group; R 2 is hydrogen, a nucleofugic group, or an optionally substituted aliphatic or aromatic group; R 3 is a nucleofugic group or an optionally substituted aliphatic or aromatic group; R 4 and R 5 are together an optionally substituted aliphatic group, and R 4 and R 5 , taken together with the intervening oxygen and boron atoms, form an optionally substituted 5- to 10-membered ring having 0 additional ring heteroatoms; and none of the variables R 1 -R 5 is substituted with a heteroaromatic group; said process comprising: (a) providing a boron “ate” complex of formula (II): where Y is a nucleofugic group; M + is a cation; and each of R 1 to R 5 is as defined above; and (b) contacting the boron “ate” complex of formula (II) with a Lewis acid under conditions that afford the boronic ester compound of formula (I) said contacting step being conducted in a reaction mixture comprising: (i) a coordinating ether solvent that has low miscibility with water; or (ii) an ether solvent that has low miscibility with water and a coordinating co-solvent, provided that the coordinating co-solvent constitutes no more than about 20% v/v of the reaction mixture; wherein the solubility of water in the ether solvent in (i) or (ii) that has low miscibility with water is less than about 5% w/w; and wherein the ether solvent in (i) or (ii) that has low miscibility with water constitutes at least about 70% v/v of the reaction mixture.