美洛昔康的合成

Synthesis of Meloxicam

糖精钠与氯乙酸甲酯缩合得 3-氧代 - 1,2 -苯并异噻唑 - 2 -乙酸甲酯 1,1-二氧化物 (2 ) ,再加甲醇钠在激烈条件下扩环 ,经 N -甲基化 ,所得 4-羟基 - 2 -甲基 - 2 H- 1,2 -苯并噻嗪 - 3-羧酸甲酯 1,1-二氧化物 (4 )再与 2 -氨基 - 5 -甲基噻唑反应得美洛昔康 (1) ,总收率为 48.6 %

Condensation of saccharin sodium with methyl chloroacetate afforded 3 oxo 1,2 benzoisothiazoline 2 acetic acid methyl ester 1,1 dioxide (2) which underwent ring enlargement under drastic conditions with sodium methoxide, then N methylation. The obtained 4 hydroxy 2 methyl 2H 1,2 benzothiazine 3 carboxylic acid methyl ester 1,1 dioxide (4) reacted with 2 amino 5 methylthiazole gave meloxicam (1) in 48.6% overall yield.\;