Synthesis of propanolamine side chain deuterated propranolol, propranolol-diol and 4-hydroxypropranol
✍ Scribed by Richard B. Walker; Wendel L. Nelson
- Publisher
- John Wiley and Sons
- Year
- 1978
- Tongue
- French
- Weight
- 336 KB
- Volume
- 14
- Category
- Article
- ISSN
- 0022-2135
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
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).