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【结 构 式】 
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【药物名称】Velaresol, 12C79, BW-12C 【化学名称】5-(2-Formyl-3-hydroxyphenoxy)pentanoic acid 【CA登记号】77858-21-0 【 分 子 式 】C12H14O5 【 分 子 量 】238.24238 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】Antianemics, HEMATOLOGIC DRUGS, Hematopoiesis Disorders Therapy |
合成路线1
The reaction of 2-hydroxy-6-methoxybenzaldehyde (I) with ethyl 5-bromopentanoate (II) by means of K2CO3 and NaI in refluxing ethanol gives ethyl 5-(2-formyl-3-methoxyphenoxy)pentanoate (III), which is hydrolyzed with NaOH in ethanol - water yielding 5-(2-formyl-3-methoxyphenoxy)pentanoic acid (IV). Finally, this compound is demethylated by treatment with BCl3 in CH2Cl2.
| 【1】 Kneen, G (Glaxo Wellcome plc); Substd. phenol ethers, their preparation, intermediates therefor, pharmaceutical compsns. containing them and the preparation thereof. EP 0022229 . |
| 【2】 Hillier, K.; Castaner, J.; Serradell, M.N.; Blancafort, P.; BW-12C. Drugs Fut 1982, 7, 9, 613. |
| 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) | 37150 | 2-Hydroxy-6-methoxybenzaldehyde | 700-44-7 | C8H8O3 | 详情 | 详情 |
| (II) | 37151 | ethyl 5-bromopentanoate | 14660-52-7 | C7H13BrO2 | 详情 | 详情 |
| (III) | 37152 | ethyl 5-(2-formyl-3-methoxyphenoxy)pentanoate | C15H20O5 | 详情 | 详情 | |
| (IV) | 37153 | 5-(2-formyl-3-methoxyphenoxy)pentanoic acid | C13H16O5 | 详情 | 详情 |
合成路线2
The reaction of 2-hydroxy-6-benzyloxybenzaldehyde (V) with ethyl 5-bromopentanoate (II) by means of K2CO3 and NaI in refluxing ethanol gives ethyl 5-(2-formyl-3-benzyloxyphenoxy)pentanoate (VI), which is hydrolyzed with KOH in ethanol yielding 5-(2-formyl-3-benzyloxyphenoxy)pentanoic acid (VII) Finally, this compound is debenzylated by hydrogenation with H2 over Pd/c in ethanol.
| 【1】 Kneen, G (Glaxo Wellcome plc); Substd. phenol ethers, their preparation, intermediates therefor, pharmaceutical compsns. containing them and the preparation thereof. EP 0022229 . |
| 【2】 Hillier, K.; Castaner, J.; Serradell, M.N.; Blancafort, P.; BW-12C. Drugs Fut 1982, 7, 9, 613. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 37151 | ethyl 5-bromopentanoate | 14660-52-7 | C7H13BrO2 | 详情 | 详情 |
| (V) | 37157 | 2-(benzyloxy)-6-hydroxybenzaldehyde | C14H12O3 | 详情 | 详情 | |
| (VI) | 37158 | ethyl 5-[3-(benzyloxy)-2-formylphenoxy]pentanoate | C21H24O5 | 详情 | 详情 | |
| (VII) | 37159 | 5-[3-(benzyloxy)-2-formylphenoxy]pentanoic acid | C19H20O5 | 详情 | 详情 |
合成路线3
The reaction of methyl 2,4-dihydroxy-3-formylbenzoate (VIII) with ethyl 5-bromopentanoate (II) by means of NaH in DMF gives ethyl 5-(2-formyl-3-hydroxy-4-methoxycarbonylphenoxy)pentanoate (IX), which is hydrolyzed with NaOH in water yielding 5-(2-formyl-3-hydroxy-4-carboxyphenoxy)pentanoic acid (X). Finally, this compound is decarboxylated by treatment with acidic alumina in refluxing dioxane-H2O or with copper in quinoline at 210 C.
| 【1】 Kneen, G (Glaxo Wellcome plc); Substd. phenol ethers, their preparation, intermediates therefor, pharmaceutical compsns. containing them and the preparation thereof. EP 0022229 . |
| 【2】 Hillier, K.; Castaner, J.; Serradell, M.N.; Blancafort, P.; BW-12C. Drugs Fut 1982, 7, 9, 613. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 37151 | ethyl 5-bromopentanoate | 14660-52-7 | C7H13BrO2 | 详情 | 详情 |
| (VIII) | 37154 | methyl 3-formyl-2,4-dihydroxybenzoate | C9H8O5 | 详情 | 详情 | |
| (IX) | 37155 | methyl 4-[(5-ethoxy-5-oxopentyl)oxy]-3-formyl-2-hydroxybenzoate | C16H20O7 | 详情 | 详情 | |
| (X) | 37156 | 4-(4-carboxybutoxy)-3-formyl-2-hydroxybenzoic acid | C13H14O7 | 详情 | 详情 |