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Synthesis of ( R, S )‐[2,3‐ 13 C 2 ]‐1‐(1′‐methyl‐2′‐pyrrolidinyl)propan‐2‐one; {( R, S )‐[2′,3′‐ 13 C 2 ]hygrine}
Author(s) -
Abraham Timothy W.,
Leete Edward
Publication year - 1996
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/(sici)1099-1344(199605)38:5<419::aid-jlcr859>3.0.co;2-l
Subject(s) - chemistry , medicinal chemistry , stereochemistry
2‐Ethoxy‐1‐methyl‐5‐pyrrolidinone (1) was reacted with ethyl [3,4‐ 13 C 2 ]‐acetoacetate (2) in the presence of TiCl 4 to give ethyl [3,4‐ 13 C 2 ]‐2‐(1′‐methyl‐5′‐oxo‐2′‐pyrrolidinyl)‐3‐oxobutanoate (3) in 85% yield. Decarboethoxylation of ethyl [3,4‐ 13 C 2 ]‐2‐(1′‐methyl‐5′‐oxo‐2′‐pyrrolidinyl)‐3‐oxobutanoate (3) was accomplished using NaCl and H 2 O in DMSO to give ( R, S )‐[2,3‐ 13 C 2 ]‐1‐(1′‐methyl‐5′‐oxo‐2′‐pyrrolidinyl)propan‐2‐one (4) in 91% yield. Protection of the ketone as a ketal (ethylene glycol, H + ), followed by reduction of the amide to the amine using LiAlH 4 and subsequent deprotection of the ketal gave ( R, S )‐[2,3‐ 13 C 2 ]‐1‐(1′‐methyl‐2′‐pyrrolidinyl)propan‐2‐one (( R, S )‐[2′,3′‐ 13 C 2 ]Hygrine) (8) in 78% yield. (61% overall yield from ethyl [3,4‐ 13 C 2 ]acetoacetate).