Premium
Synthesis of propanolamine side chain deuterated propranolol, propranolol‐diol and 4‐hydroxypropranol
Author(s) -
Walker Richard B.,
Nelson Wendel L.
Publication year - 1978
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580140616
Subject(s) - epichlorohydrin , chemistry , isopropylamine , epoxide , pyridine , diol , hydrolysis , glycidol , catalysis , nuclear chemistry , polymer chemistry , organic chemistry
Syntheses of 1‐(isopropylamino)‐3‐(1‐naphthyloxy)‐2‐propanol‐1,1,2,3,3‐d 5 ( 1 ), 3‐(1‐naphthyloxy)‐1,2‐propanediol‐1,1,2,3,3‐d5 ( 2 ) and 1‐(isopropylamino)‐3‐(4‐hydroxy‐1‐naphthyloxy)‐2‐propanol‐1,1,2,3,3‐d5 ( 3 ) from epichlorohydrin‐d5 are described. Treatment of epichlorohydrin‐d5 with 1‐naphthol, in the presence of a catalytic amount of pyridine, afforded a mixture of 1‐chloro‐3‐(1‐naphthyloxy)‐2‐propanol‐1,1,2,3,3‐d5 ( 4 ) and 1,2‐epoxy‐(1‐naphthyloxy)‐propane‐1,1,2,3,3‐d5 which was converted to 4, with HCl or to 5 with 6 N KOH. Reaction of 4 with isopropylamine afforded 1. Acid catalyzed hydrolysis of 5 afforded 2. A modification of the synthesis of 1 using 4‐methoxy‐1‐naphthol, epichlorohydrin‐d5 (1 N NaOH) afforded epoxide 7, which was opened with isopropylamine. Ether cleavage with pyridine HCl completed synthesis of 1‐(isopropylamino)‐3‐(4‐hydroxy‐1‐naphthyloxy)‐2‐propanol‐1,1,2,3,3‐d5 ( 3 ).