Prodn. of methyl 5-bromo-6-methoxy-1-naphthoate - used as tolrestat intermediate, comprises reaction of methyl 6-methoxy-1-naphthoate with bromine in presence of oxidising agent

摘要

Prodn. of methyl 5-bromo-6-methoxy-1-naphthoate of formula (I) comprises reacting methyl 6-methoxy-1-naphthoate of formula (II) with bromine in the molar ratio 1:0.5-0.6 in a solvent at 0 deg. C to the b.pt. of the mixt. agent which oxidises HBr to Br2. USE/ADVANTAGE - (I) is an intermediate for the antidiabetic aldose reductase inhibitor tolrestat (see EP 59596, EP 200840, EP 307519 and US 4088748). Compared with the processes known from EP 200840 and EP 59596, the method is simpler, gives (I) in higher yields (about 90%) and purity (above 98%), and provides ecological and economical advantages as well as a healthier working environment by avoiding the use of chlorinated hydrocarbon solvents and excess bromine (also see "Example").