非达司他的合成

Synthesis of Fidarestat

以对氟苯甲醚为原料,经傅-克酰化及分子内闭环反应制得(±)-6-氟-3,4-二氢-4-氧代-2H-1-苯并吡喃-2-甲酸(4),用(R)-N-苄基-1-苯乙胺(5)拆分得到(2S)-型的4a。再经Bucherer-Bergs反应、酯化及氨解反应制得非达司他,总收率约17%。

Fidarestat was synthesized from 4-fluoroanisole via Friedel-Crafts acylation and cyclization to give （±）-6-fluoro-3,4-dihydro-4-oxo-2H-l-benzopyran-2-carboxylic acid（4）, which was subjected to resolution with （R）- N-benzyl-l-phenylethylamine （5） to form the （2S）-isomer（4a）, followed by Bucherer-Bergs reaction, esterification and aminolysis with an overall yield of about 17 %.