Synthesis of tritium labeled MK-886, a leukotriene biosynthesis inhibitor; employment of epibromohydrin as a masked electrophilic acetone synthon

1-(4-Chloro-[3-3H]benzyl) -3-(t-butylthio)-a, a-dimethyl-5-(i-propyl) -indole-2-propanoic acid (10, MK-886) was prepared by catalytic tritium/halogen exchange on 1-(4-chloro-3-iodobenzyl)-3-(t-butylthio)-a,a -dimethyl-5-(i-propyl)-indole-2-propanoic acid (9). Compound 9 was prepared by a synthesis converging at the indole benzylation step. The required indole 4 was prepared by means of a Fischer indole synthesis employing the highly functionalized unsymmetrical ketone 3. Ketone 3 was efficiently made in three steps using epibromohydrin as a masked electrophilic acetone synthon. The halogenated benzyl bromide moiety 7 was prepared in three steps from 1-chloro-2-iodo-4-(trifluoromethyl)-benzene.