【摘要】 以3-氨基-2-噻吩甲酸甲酯为原料,经氯磺化、甲胺化、N-烷基化、环合等反应合成了替诺昔康的中间体4-羟基-3-甲基-2H-噻吩并[2,3-e]-1,2-噻嗪-2-羧酸甲酯-1,1-二氧化物(MHTTCD)。氯磺化时在大大减少溶剂(醋酸)用量的条件下,收率为78%,甲胺化收率为81.6%。环合反应在甲醇钠的甲醇溶液中进行,合适的甲醇钠浓度为1mol/L。回流反应1h,该步收率达55.5%。合成路线反应总收率为11.11%。通过GC-MS确认了各中间体的结构。由于N-烷基化时以氯乙酸乙酯代替肌氨酸乙酯盐酸盐以及收率的提高,降低了合成成本。更多还原

【Abstract】 The intermediate of Tinoxicam,4-hydroxy-3-methyl-2H-thieno-1,2-thiazine-2-(methyl) carboxylate-1,1-dioxide(MHTTCD) was synthesized from methyl 3-amino-2-thiophene methyl carboxylate through four steps: chlorosulfonylation,methylamination,N-alkylation,and cyclization.The solvent,acetic acid was greatly reduced in the chlorosulfonylation step, and the yield of 78% was obtained.The yield for methylamination was 81.6% with the aqueous methylamine as the reagent.The cyclization was carried out in the methanol solution of sodium methylate with the appropriate concentration of 1mol/L,and the yield of 55.5% was obtained after reacting for 1 hour.The total yield was 11.11%.The structures of the intermediates were confirmed by MS.The production cost was lowed on account of the replacement of ethyl sarcosinate hydrochloride by ethyl chloroacetate in the process of N-alkylation and the increase of yield.更多还原