By cyclization of 2-amino-6-fluorobenzonitrile (I) with bicyclo[3.1.1]heptan-2-one (II) by means of ZnCl2 at 110-20 C.
The synthesis of [9-14C]-SM-10888 has been described: The carboxylation of 1,3-difluorobenzene (I) with labeled CO2 by means of butyllithium in THF gives 2,6-difluorobenzoic acid (II), which by reaction first with SOCl2 and then with NH4OH yields the corresponding amide (III). The reaction of (III) with SOCl2 in hot DMF affords the nitrile (IV), which by reaction with ammonia in ethanol at 135 C gives 2-amino-6-fluorobenzonitrile (VI). Finally, this compound is cyclized with bicyclo[3.3.1]heptan-2-one (VI) by means of ZnCl2 at 105 C in nitrobenzene.