Efficient synthesis of an androgen receptor modulator

Abstract An efficient synthesis of the androgen receptor modulator ( R )- 4a having an 8 H -[1,4]oxazino[2,3- f ]quinolin-8-one skeleton is described. Synthesis of this ring system, not readily accessible by classical Knorr cyclization methodology, was accomplished by an ortho -metallation strategy. Thus, lithiation of a pivaloyl-protected 7-amino-3,4-dihydro-1,4-benzoxazine using n -butyllithium allowed the introduction of a trifluoroacetyl group regioselectively at the 8-position. Subsequent Wittig reaction and acid catalyzed cyclization afforded the desired 8 H -[1,4]oxazino[2,3- f ]quinolin-8-one ( R )- 4a in very good overall yield from the corresponding benzoxazine.