Premium
Synthesis of 3‐alkylcarbonyloxymethyl derivatives of 5‐fluorouracil
Author(s) -
Roberts William J.,
Sloan Kenneth B.
Publication year - 2002
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570390509
Subject(s) - chemistry , alkylation , yield (engineering) , methylamine , bromide , iodide , fluorouracil , column chromatography , organic chemistry , benzyl bromide , catalysis , medicine , materials science , surgery , chemotherapy , metallurgy
3‐Alkylcarbonyloxymethyl derivatives of 5‐fluorouracil have been synthesized starting with 1‐ethyloxy‐carbonyl‐5‐fluorouracil. Alkylation of the starting material with alkylcarbonyloxymethyl iodides, generated from the corresponding chlorides by the Finkelstein reaction, in the presence of 1,8‐bis(dimethyl‐amino)naphthalene followed by deprotection with 1,1‐dimethylethylamine gave good yields (50‐60%) of the target derivatives after column chromatography. A 90% yield of 3‐acetyloxymethyl‐5‐fluorouracil was obtained when the corresponding commercially available bromide was used, instead of the in situ generated iodide, and the product could be isolated from the crude reaction by crystallization. An alternate path of sequential alkylation of 5‐fluorouracil with alkylcarbonyloxymethyl chlorides in the presence of tertiary amines, exhibiting different reactivities towards the chlorides, gave an excellent yield of 1‐acetyloxymethyl‐3‐propionyloxymethyl‐5‐fluorouracil in the one instance it was attempted, but subsequent deprotection of the 1‐position with methylamine gave only a 24% yield of 3‐propionyloxymethyl‐5‐fluorouracil.