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【结 构 式】 
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【分子编号】68759 【品名】(E)-3-((E)-5-(hydroxyimino)cyclohex-1-en-1-yl)acrylic acid 【CA登记号】 |
【 分 子 式 】C9H11NO3 【 分 子 量 】181.19128 【元素组成】C 59.66% H 6.12% N 7.73% O 26.49% |
合成路线1
该中间体在本合成路线中的序号：(LXVI)Conjugate addition of acrolein (LVIII) to nitromethane in the presence of KOH in MeOH followed by treatment with Na2S2O5 in H2O gives the nitrodisulfonate (LIX), which is hydrolyzed with glyoxylic acid by means of NaHCO3 to yield 4-nitroheptanedial (LX). Compound (LX) is cyclized in the presence of pyrrolidine and PhCOOH in CH2Cl2, providing 5-nitro-1-cyclohexenecarbaldehyde (LXI). Wittig reaction of aldehyde (LXI) with (methoxycarbonylmethylene)triphenylphosphorane (LXII) leads to conjugated ester (LXIII), which is finally saponified with NaOH .
Acid (XXXVII) can be alternatively prepared by Knoevenagel condensation of aldehyde (LXI) with malonic acid (LXIV) .
Hydrolysis of ethylene ketal (XVI) with aqueous p-toluenesulfonic acid gives ketone (LXV), which, without isolation, is converted to oxime (LXVI) by addition of hydroxylamine hydrochloride. Subsequent oxidation of oxime (LXVI) using sodium molybdate and H2O2 leads to compound (XXXVII) .
| 【1】 Wu, G., Sudhakar, A.R., Wang, T. et al. (Schering Corp.). Exo- and diastereo- selective synthesis of himbacine analogs. CA 2594871, EP 1848705, EP 2196454, EP 2196468, EP 2206697, JP 2008526972, US 2006247450, WO 2006076415. |
| 【2】 Thiruvengadam, T.K., Wang, T., Chiu, J.S., Liao, J. (Schering Corp.). Synthesis of 3-(5-nitrocyclohex-1-enyl)acrylic acid and esters thereof. EP 2035364, JP 2009542675, US 2008009651, WO 2008005344. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVI) | 68716 | (E)-3-(1,4-dioxaspiro[4.5]dec-7-en-7-yl)acrylic acid | C11H14O4 | 详情 | 详情 | |
| (XXXVII) | 68733 | (E)-3-(5-nitrocyclohex-1-en-1-yl)acrylic acid;3-(5-nitro-1-cyclohexenyl)-2-propenoic acid | C9H11NO4 | 详情 | 详情 | |
| (LVIII) | 17668 | acrylaldehyde; Acrolein | 107-02-8 | C3H4O | 详情 | 详情 |
| (LIX) | 68754 | sodium 1,7-dihydroxy-4-nitroheptane-1,7-disulfonate | C7H13NNa2O10S2 | 详情 | 详情 | |
| (LX) | 68755 | 4-nitroheptanedial | C7H11NO4 | 详情 | 详情 | |
| (LXI) | 68756 | 5-nitro-1-cyclohexenecarbaldehyde | C7H9NO3 | 详情 | 详情 | |
| (LXII) | 14689 | Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate | 2605-67-6 | C21H19O2P | 详情 | 详情 |
| (LXIII) | 68757 | (E)-methyl 3-(5-nitrocyclohex-1-en-1-yl)acrylate | C10H13NO4 | 详情 | 详情 | |
| (LXIV) | 12963 | Malonic acid | 141-82-2 | C3H4O4 | 详情 | 详情 |
| (LXV) | 68758 | (E)-3-(5-oxocyclohex-1-en-1-yl)acrylic acid | C9H10O3 | 详情 | 详情 | |
| (LXVI) | 68759 | (E)-3-((E)-5-(hydroxyimino)cyclohex-1-en-1-yl)acrylic acid | C9H11NO3 | 详情 | 详情 |