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【结 构 式】 
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【分子编号】57443 【品名】3-(3,4-dimethoxyphenyl)-4,5,6-trimethoxy-2-benzofuran-1(3H)-one 【CA登记号】 |
【 分 子 式 】C19H20O7 【 分 子 量 】360.3636 【元素组成】C 63.33% H 5.59% O 31.08% |
合成路线1
该中间体在本合成路线中的序号：(V)A different synthetic strategy requires the precursor phthalide derivative (V), which is prepared by two related ways. 3,4,5-Trimethoxybenzoyl chloride (I) is condensed with 2-amino-2-methyl-1-propanol (II), and the resultant hydroxy amide is further cyclized with SOCl2 to the oxazoline (III). Lithiation of (III), followed by addition to veratraldehyde (IV) and acidic oxazoline hydrolysis, leads to the target lactone (V). Alternatively, isobenzofuranone (V) is obtained by direct condensation between trimethoxybenzoic acid (VI) and veratraldehyde (IV) in the presence of polyphosphoric acid.
| 【1】 Mori, S.; et al.; Convergent synthesis of S-8921, a new potent hypocholesterolemic arylnapththalene lignan analog. Tetrahedron Lett 1999, 40, 6, 1165. |
| 【2】 Mori, S.; Takechi, S.; Kida, S. (Shionogi & Co. Ltd.); Process for producing lignan cpd.. EP 0646570; WO 9424087 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 13571 | 3,4,5Ttrimethoxybenzoyl chloride | 4521-61-3 | C10H11ClO4 | 详情 | 详情 |
| (II) | 21513 | 2-amino-2-methyl-1-propanol；Karl Fischer;2-Amino-2-methyl-propan-1-ol；2-amino-2-methyl-1-propanol | 124-68-5 | C4H11NO | 详情 | 详情 |
| (III) | 57442 | 4-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-2,6-dimethoxyphenyl methyl ether; 4,4-dimethyl-2-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1,3-oxazole | C14H19NO4 | 详情 | 详情 | |
| (IV) | 18304 | 3,4-Dimethoxybenzaldehyde; Veratraldehyde | 120-14-9 | C9H10O3 | 详情 | 详情 |
| (V) | 57443 | 3-(3,4-dimethoxyphenyl)-4,5,6-trimethoxy-2-benzofuran-1(3H)-one | C19H20O7 | 详情 | 详情 | |
| (VI) | 32225 | 3,4,5-trimethoxybenzoic acid | 118-41-2 | C10H12O5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XI)Addition of the lithium acetylide prepared from methyl propiolate (VIII) to 3-ethylpentanal (VII) gives methyl 6-ethyl-4-hydroxy-2-octynoate (IX), which is further oxidized to the corresponding keto ester (X) employing the Jones reagent in acetone. Cycloaddition between alkyne (X) and the lithium derivative of the isobenzofuranone (V) gives rise to the 1,4-epoxy dihydronaphthalene adduct (XI). Subsequent acidic hydrolysis of (XI) furnishes the hydroxy naphthalenone (XII). Finally, reductive aromatization of (XII) using TiCl3 produces the title naphthol compound.
| 【1】 Mori, S.; Takechi, S.; Kida, S. (Shionogi & Co. Ltd.); Process for producing lignan cpd.. EP 0646570; WO 9424087 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 57444 | 3-ethylpentanal | C7H14O | 详情 | 详情 | |
| (VIII) | 19588 | methyl propiolate | 922-67-8 | C4H4O2 | 详情 | 详情 |
| (IX) | 57445 | methyl 6-ethyl-4-hydroxy-2-octynoate | C11H18O3 | 详情 | 详情 | |
| (X) | 57432 | methyl 6-ethyl-4-oxo-2-octynoate | C11H16O3 | 详情 | 详情 | |
| (XI) | 57443 | 3-(3,4-dimethoxyphenyl)-4,5,6-trimethoxy-2-benzofuran-1(3H)-one | C19H20O7 | 详情 | 详情 | |
| (XII) | 57446 | methyl 8-(3,4-dimethoxyphenyl)-10-(3-ethylpentanoyl)-4,5,6-trimethoxy-1-[(trimethylsilyl)oxy]-11-oxatricyclo[6.2.1.0~2,7~]undeca-2,4,6,9-tetraene-9-carboxylate | C33H44O10Si | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IX)In a related procedure, malic acid (I) is converted into the O-acetylated monomethyl ester (IV) by a sequence involving O-acetylation with acetic anhydride, followed by dehydration of the resultant O-acetyl malic acid (II) to the cyclic anhydride (III), which undergoes further methanolysis to mono ester (IV). Mono-acid (IV) is then chlorinated with SOCl2, yielding acid chloride (V). Subsequent Li2CuCl4-catalyzed cross-coupling of acid chloride (V) with 2-ethylbutylmagnesium bromide (VI) affords ketone (VII). Elimination of the acetate group of (VII) with triethylamine in toluene leads to the acyl propenoate (VIII). This is subjected to cycloaddition reaction with the lithium derivative of phthalide (IX) producing the dihydroxydihydronaphthalene adduct (X). Finally, dehydration of (X) under acidic conditions furnishes the title compound.
| 【1】 Mori, S.; et al.; Convergent synthesis of S-8921, a new potent hypocholesterolemic arylnapththalene lignan analog. Tetrahedron Lett 1999, 40, 6, 1165. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 22743 | Hydroxysuccinic acid; Malic acid; Hydroxybutanedioic acid | 617-48-1 | C4H6O5 | 详情 | 详情 |
| (II) | 57448 | 2-(acetyloxy)succinic acid | C6H8O6 | 详情 | 详情 | |
| (III) | 57449 | 2,5-dioxotetrahydro-3-furanyl acetate | C6H6O5 | 详情 | 详情 | |
| (IV) | 57450 | 3-(acetyloxy)-4-methoxy-4-oxobutanoic acid | C7H10O6 | 详情 | 详情 | |
| (V) | 57451 | methyl 2-(acetyloxy)-4-chloro-4-oxobutanoate | C7H9ClO5 | 详情 | 详情 | |
| (VI) | 57441 | bromo(2-ethylbutyl)magnesium | C6H13BrMg | 详情 | 详情 | |
| (VII) | 57452 | methyl 2-(acetyloxy)-6-ethyl-4-oxooctanoate | C13H22O5 | 详情 | 详情 | |
| (VIII) | 57453 | methyl (E)-6-ethyl-4-oxo-2-octenoate | C11H18O3 | 详情 | 详情 | |
| (IX) | 57443 | 3-(3,4-dimethoxyphenyl)-4,5,6-trimethoxy-2-benzofuran-1(3H)-one | C19H20O7 | 详情 | 详情 | |
| (X) | 57454 | methyl (1S,2R)-1-(3,4-dimethoxyphenyl)-3-(3-ethylpentanoyl)-1,4-dihydroxy-6,7,8-trimethoxy-1,2-dihydro-2-naphthalenecarboxylate | C30H38O10 | 详情 | 详情 |