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

Abstract A simple synthetic route has been developed to prepare 1′- H -spiro(indoline-3,4′-piperidine) ( 1d ). Dialkylation of 2-fluorophenylacetonitrile with N -( tert -butyloxycarbonyl)-bis(2-chloroethyl)amine ( 5 ) gave 6 . Deprotection of Boc followed by cyclization resulted 1d in 67% overall yield. Selective Boc or Cbz protection of 1′- N gave 1a or 1b with 90 and 85% yield, respectively. Thus, in a five-step procedure, 1a and 1b were synthesized from commercially available reagents in over 50% overall yield. All 3 compounds ( 1a , 1b and 1d ) can be utilized as templates to synthesize compounds for GPCR targets.