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Synthesis of 1,3,5‐trimethoxy[1‐ 14 C]benzene
Author(s) -
Lee Helen T.,
Travalent Annette M.,
Woo Peter W. K.
Publication year - 1990
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.2580281006
Subject(s) - chemistry , malonic acid , sodium methoxide , oxalyl chloride , dimethyl sulfate , medicinal chemistry , sulfuric acid , sodium , pyran , organic chemistry , methanol
Utilizing the facile acylative annulation of 2‐methoxypropene with [1‐ 14 C]malonyl dichloride ( 5 ), the synthesis of 1,3,5‐trimethoxy[1‐ 14 C]benzene ( 8 ) was accomplished through a seven‐step sequence starting from potassium [ 14 C]cyanide with an overall yield of 60%. Thus, reaction of bromoacetic acid with potassium [ 14 C]cyanide gave sodium [ 14 C]cyanoacetate ( 1 ). Hydrolysis of 1 with sodium hydroxide solution provided the sodium salt of [1‐ 14 C]malonic acid ( 2 ). Treatment of 2 with calcium chloride gave the calcium salt 3 , which was acidified with concentrated sulfuric acid in ether to give [1‐ 14 C]malonic acid ( 4 ). Reaction of 4 with oxalyl chloride in refluxing ether gave [1‐ 14 C]malonyl dichloride ( 5 ). Annulative acylations of 2‐methoxypropene with 5 gave the crucial intermediate 5‐methoxy[1‐ 14 C]resorcinol ( 7 ), together with 4‐hydroxy‐6‐methyl‐[2 (or 4)‐ 14 C]2H‐pyran‐2‐one ( 6 ), in a ratio of 3: 1. However, 6 could be advantageously converted to 7a by initial 0‐methylation with dimethyl sulfate, followed by rearrangement of the product, 4‐methoxy‐6‐methyl[2(or 4)‐ 14 C]2H‐pyran‐2‐one ( 6a ), upon treatment with sodium methoxide. Finally, bis ‐ 0 ‐methylation of 7 and 7a with dimethyl sulfate in refluxing acetone gave the title compound 8 .