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Synthesis of (R)‐ and (S)‐amphetamine‐d 3 from the corresponding phenylalanines
Author(s) -
Gal Joseph
Publication year - 1977
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.2580130101
Subject(s) - chemistry , yield (engineering) , lithium (medication) , enantiomer , aluminum hydride , medicinal chemistry , alanine , amino acid , alcohol , chloride , naphthalene , enantioselective synthesis , enantiomeric excess , stereochemistry , organic chemistry , ion , catalysis , medicine , biochemistry , materials science , metallurgy , endocrinology , methoxide
The synthesis of (R)‐(−)‐ and (S)‐(+)‐2‐amino‐1‐phenylpropane‐3,3,3‐d 3 via a modification of a published procedure for the unlabelled compounds is described. The preparation of the (S)enantiomer involved in the first step the reduction of D‐phenyl‐alanine to (R)‐2‐amino‐3‐phenyl‐1‐propanol–1,1‐d 2 with lithium aluminum deuteride. The reduction product was treated with p‐toluenesulfonyl chloride to give (R)‐3‐phenyl–2‐(4‐toluenesulfamoyl)propyl–1,1‐d 2 4‐toluenesulfonate, which was reduced with lithium aluminum deuteride to (S)‐N‐(1‐methyl‐d 3 ‐2‐phenethyl)‐4‐toluenesulfonamide. The latter compound was cleaved to (S)‐(+)‐2‐amino‐1‐phenylpropane‐3,3,3‐d 3 using naphthalene anion radical. The overall yield in the sequence was 32.8%, the isotopic purity of the product was 99%, and the enantiomeric purity > 99%. The methyl ester of the amino acid could also be used as starting material in the synthesis.