【结 构 式】 |
【分子编号】29158 【品名】ethyl 5-[(2-fluorophenyl)(hydroxyimino)methyl]-6-hydroxy-2,3-dihydro-1-benzofuran-2-carboxylate 【CA登记号】 |
【 分 子 式 】C18H16FNO5 【 分 子 量 】345.3271832 【元素组成】C 62.61% H 4.67% F 5.5% N 4.06% O 23.17% |
合成路线1
该中间体在本合成路线中的序号:(IV)Catalytic hydrogenation of banzofuran (I) produces high yields of the dihydrobenzofuran (II) with some contamination of fully saturated material. Use of excess AlCl3 at room temperature during the Friedel Crafts' acylation step cleaves the methyl ether, and treatment of the crude product with HBr in acetic acid gives (III) in 93% overall yield. The oximation reaction requires prolonged heating with excess hydroxylamine hydrochloride, but after esterification of the crude oxime, a 90% yield of (IV) is obtained. In the cyclization leading to isoxazole (V) the presence of pyridine increases the reaction rate and reduces formation of an oxazole, isomeric with (V), which apparently occurs from a Beckmann rearrangement with intramolecular capture by the phenol. Treatment of the crude oxime acetate with K2CO3 in DMF at 60 C gives the isoxazole (V) cleanly, in high yield. The remarkable step in this synthesis is the facile chlorination of (V) with trichloroisocyanuric acid (B), utilizing all three chlorines from the reagent, leading to pure title compound in nearly quantitative yield.
【1】 Mannhold, R.; ABBOTT-53385. Drugs Fut 1985, 10, 5, 363. |
【2】 Bunnell, P.R.; Plattner, J.J.; Fung, A.K.L.; et al.; Synthesis and pharmacological evaluation of Abbott (A)-53385: A new high ceiling salidiuretic and uricosuric agent. Diuretics 1984, 374-81. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(A) | 19551 | 2-Fluorobenzoyl chloride | 393-52-2 | C7H4ClFO | 详情 | 详情 |
(B) | 19555 | 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione | 87-90-1 | C3Cl3N3O3 | 详情 | 详情 |
(I) | 29156 | ethyl 6-methoxy-1-benzofuran-2-carboxylate | C12H12O4 | 详情 | 详情 | |
(II) | 19550 | ethyl 6-methoxy-2,3-dihydro-1-benzofuran-2-carboxylate | C12H14O4 | 详情 | 详情 | |
(III) | 29157 | 5-(2-fluorobenzoyl)-6-hydroxy-2,3-dihydro-1-benzofuran-2-carboxylic acid | C16H11FO5 | 详情 | 详情 | |
(IV) | 29158 | ethyl 5-[(2-fluorophenyl)(hydroxyimino)methyl]-6-hydroxy-2,3-dihydro-1-benzofuran-2-carboxylate | C18H16FNO5 | 详情 | 详情 | |
(V) | 19554 | ethyl 3-(2-fluorophenyl)-5,6-dihydrofuro[3,2-f][1,2]benzisoxazole-6-carboxylate | C18H14FNO4 | 详情 | 详情 |