Synthesis of 4-(R)-naphthalen-2-oxy-1-(1-phenyl-(S)-ethyl)-pyrrolidin-3-(R)-ol and 4-(S)-naphthalen-2-yloxy-1-(1-phenyl-(S)-ethyl)-pyrrolidin-3-(S)-ol: Versatile chiral intermediates for synthesis

ORGN 671

Daniel D. Holsworth1, Michael A. Stier2, Wei Wang1, Jeremy J Edmunds1, Tingsheng Li3, and Samarendra Maiti3. (1) Michigan Laboratories, Pfizer Global Research & Development, 2800 Plymouth Road, Ann Arbor, MI 48105, (2) Michigan Laboratories, Pfizer Global Research and Development, Michigan Laboratories - Ann Arbor, 2800 Plymouth Road, Ann Arbor, MI 48105, (3) Naeja Pharmaceuticals, Edmonton, AB T6E 5V2, Canada
A convenient and rapid synthesis of 4-(R)-(naphthalen-2-yloxy)-1-(1-phenyl-(S)-ethyl)-pyrrolidin-3-(R)-ol (Compound 1) and 4-(S)-(naphthalen-2-yloxy)-1-(1-phenyl-(S)-ethyl)-pyrrolidin-3-(S)-ol (Compound 2) is disclosed. The reaction scheme is highlighted by meso-epoxidation of 1-(1-phenyl-(S)-ethyl)-2,5-dihydro-1H-pyrrole followed by addition of 2-naphthol alkoxide to provide both expected diastereoisomers. Separation of the diastereoisomers by crystallization provided access to both diastereoisomers in modest yield without the employment of expensive chiral catalysts. An X-ray structure of Compound 1 was obtained to unambiguously assign the stereochemistry. These chiral pyrrolidine analogs should be useful as intermediates in natural product, combinatorial/parallel synthesis, and medicinal chemistry.

 

New Reactions, Methodology, Heterocycles, Aromatics
8:00 PM-10:00 PM, Wednesday, August 25, 2004 Pennsylvania Convention Center -- Hall D, Poster

Division of Organic Chemistry

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004