【摘要】 为了研究氟雷拉纳适合于工业化生产的合成方法，以2-氟甲苯为起始原料，经乙酰氯酰化，氰化钠氰基取代和硫酸水解得到4-乙酰基-2-甲基苯甲酸，然后在三乙胺的作用下，与3’,5’-二氯-2,2,2-三氟苯乙酮经缩合，脱水，环化得到中间体4-(5-(3,5-二氯苯基)5-三氟甲基-4,5-二氢异■唑-3-基)-2-甲基苯甲酸；以甘氨酸为原料，在碱Na OH作用下，与二碳酸二叔丁酯反应生成2-(叔丁氧基羰基氨基)乙酸，然后在N,N-羰基二咪唑和4-二甲胺吡啶的催化下，与三氟乙胺反应，随后通入干燥盐酸气体，得到中间体2-氨基-N-(2,2,2-三氟乙基)乙酰胺盐酸盐；最后两中间体经酰胺化反应合成目标产物氟雷拉纳，产率达86.7%。该合成工艺原料易得，价格便宜，目标产物的产率高，适用于氟雷拉钠工业化合成。更多还原

【Abstract】 A synthetic method suitable for industrial fluralaner was studied. 4-acetyl-2-methylbenzoic acid was prepared by using 2-fluorotoluene as the starting material through these reations of acetylation, cyano substitution and hydrolysis,then under the action of triethylamine,4-acetyl-2-methylbenzoic acid condensed with 3’,5’-dichloro-2,2,2-trifluoroacetophenone, following being dehydrated, and cyclized to give the intermediate 4-(5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid. In the present of NaOH, glycine reacted with di-tert-butyl dicarbonate to give the 2-(tert-butoxycarbonylamino)acetic acid, then under the catalysis of N,N-carbonyldiimidazole and 4-dimethylaminopyridine, 2-(tert-butoxycarbonylamino)acetic acid, reacted with trifluoroethylamine and hydrogen chloride to give the2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride. Finally, fluralaner was prepared by the reaction of 4-(5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid with 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride. The content of products was 86.7%. The process technology was suitable for industrial fluralaner with readily available, inexpensive material and high content of products.更多还原