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Derivatives of β‐adrenergic antagonists. Preparation of propranolol‐3,3‐ 2 H 2 and propranolol‐ 18 O
Author(s) -
Nelson Wendel L.,
Bartels Michael J.
Publication year - 1983
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.2580201002
Subject(s) - isopropylamine , chemistry , pyridine , epichlorohydrin , medicinal chemistry , yield (engineering) , propranolol , nuclear chemistry , propane , organic chemistry , medicine , materials science , metallurgy
Syntheses of 1‐(isopropylamino)‐3‐(1‐naphthoxy)‐2‐propanol‐3,3‐ 2 H 2 (propranolol‐3,3‐ 2 H 2 ) ( 1 ) and of 1‐(isopropylamino)‐3‐(1‐naphthoxy‐ 18 0)‐2‐propanol (propranolol‐ 18 0) ( 2 ) are described. Reaction of 1‐naphthol ( 3 ) with glycerol‐2,3‐acetonide‐1,1‐ 2 H 2 tosylate ( 4 ) afforded, after hydrolysis, 3‐(1‐naphthoxy)propane‐1,2‐diol‐3,3‐ 2 H 2 ( 5 ). Tosylation afforded the primary tosylate ( 6 ) which was converted into 3‐(1‐naphthoxy)‐1,2‐epoxypropane‐3,3‐ 2 H 2 ( 7 ). Reaction of 7 with isopropylamine afforded 1 in 31% overall yield from 4 . Reaction of 1‐naphthol‐ 18 0 ( 8 ) with epichlorohydrin (pyridine) afforded a mixture of 1‐chloro‐3‐(1‐naphthoxy‐ 18 0)‐2‐propanol ( 9 ) and 1,2‐epoxy‐3‐(1‐naphthoxy‐ 18 0)propane ( 10 ), which was converted to chlorohydrin 9 with HCl. Reaction of 9 with isopropylamine afforded 2 in 60% overall yield from 1‐naphthol‐ 18 0.