Preparation of 1,5-methano-2,3,4,5- tetrahydro-1H-3-benzazepine via Pd-catalyzed cyclization.
[reaction: see text] A new approach to prepare 1,5-methano-2,3,4,5-tetrahydro-1H-3-benzanepine (1) is discussed. This strategy utilized a tandem Michael addition and Pd-catalyzed cyclization to afford cyanobenzofulvene acetal 13. This indene intermediate (13) was subjected to hydrogenolysis to provide an amino ester (12) and was cyclized with base to afford lactam 5. The lactam (5) was reduced with borane to afford the desired benzazepine (1).
Singer
Robert A
RA
Chemical Research and Development, Pfizer Global Research and Development, Pfizer, Inc., Eastern Point Road, Groton, Connecticut 06340, USA. singerra@groton.pfizer.com
McKinley
Jason D
JD
Barbe
Guillaume
G
Farlow
Robin A
RA
D001552:Benzazepines / Q000138:chemical synthesis*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D007202:Indicators and Reagents; D007769:Lactams / Q000737:chemistry*; D008697:Methane / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*
D001552:Benzazepines; D007202:Indicators and Reagents; D007769:Lactams; D010165:Palladium; D008697:Methane