A convenient synthesis of 1′-H-spiro-(indoline-3,4′-piperidine) and its derivatives

A simple synthetic route has been developed to prepare 1′-H-spiro(indoline-3,4′-piperidine) (). Dialkylation of 2-fluorophenylacetonitrile with N-(tert-butyloxycarbonyl)-bis(2-chloroethyl)amine () gave . Deprotection of Boc followed by cyclization resulted in 67% overall yield. Selective Boc or Cbz protection of 1′-N gave or with 90 and 85% yield, respectively. Thus, in a five-step procedure, and were synthesized from commercially available reagents in over 50% overall yield. All 3 compounds (, and ) can be utilized as templates to synthesize compounds for GPCR targets.