PROBES FOR NARCOTIC RECEPTOR MEDIATED PHENOMENA. 38.1 AN EXPEDITIOUS SYNTHESIS OF RAC-CIS-4a-ETHYL-2-METHYL-1,2,3,4,4a,9a-HEXAHYDROBENZOFURO[2,3-c]PYRIDIN-6-OL AND RAC-CIS-2-METHYL-4a-PHENETHYL-1,2,3,4,4a,9a-HEXAHYDROBENZOFURO [2,3-c]PYRIDIN-6-OL

摘要

A high-yielding five-step synthesis of cis-benzofuropyridin-6-ols provided an improved route to compounds with low to subnanomolar affinity at opioid receptors and high antinociceptive potency. This synthesis provided the known rac-cis-4a-ethyl-2-memyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol (1a) in high yield, and the novel rac-cis-2-methyl-4a-phenethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol (1b). It was achieved using NBS to prepare the key intermediate 7. Di-demethylation followed by subsequent displacement of the bromine by the phenolic ion in hot Et3N gave the desired la. The structure of 1a was confirmed by X-ray crystallography.