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【结 构 式】 
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【分子编号】38418 【品名】methyl 4-piperidinecarboxylate; Isonipecotic acid methyl ester; 4-piperidinecarboxylic acid methyl ester 【CA登记号】2971-79-1 |
【 分 子 式 】C7H13NO2 【 分 子 量 】143.18576 【元素组成】C 58.72% H 9.15% N 9.78% O 22.35% |
合成路线1
该中间体在本合成路线中的序号：(III)The reaction of piperidine-4-carboxylic acid (I) with SOCl2 gives the acyl chloride (II), which is treated with methanol to yield the methyl ester (III). Finally, this compound is condensed with 4-chloro-1-(4-fluorophenyl)-1-butanone (IV) by means of K2CO3 in refluxing acetone.
| 【1】 Kar, K.; Pandey, S.K.; Tripathi, R.C.; Saxena, A.K.; Synthesis and SAR studies of 1-substituted-n-(4-alkoxycarbonylpiperidin-1-yl)alkanes as potent antiarrhythmic agents. Bioorg Med Chem Lett 1999, 9, 18, 2693. |
| 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) | 17402 | 4-nipecotic acid;piperidine-4-carboxylic acid;p-nipecotic acid; Isonipecotic acid; Hexahydroisonicotinic acid; 4-Piperidinecarboxylic acid | 498-94-2 | C6H11NO2 | 详情 | 详情 |
| (II) | 38417 | 4-piperidinecarbonyl chloride | C6H10ClNO | 详情 | 详情 | |
| (III) | 38418 | methyl 4-piperidinecarboxylate; Isonipecotic acid methyl ester; 4-piperidinecarboxylic acid methyl ester | 2971-79-1 | C7H13NO2 | 详情 | 详情 |
| (IV) | 35864 | 4-chloro-1-(4-fluorophenyl)-1-butanone | 3874-54-2 | C10H10ClFO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVII)In a related method, electrophilic bromination of 2,3-dichlorophenol (XI) gave (XII). Heck reaction of bromide (XII) with methyl acrylate (XIII) produced the cinnamic acid derivative (XIV). Sulfonylation of the phenolic hydroxyl of (XIV) with trifluoromethanesulfonic anhydride in pyridine furnished the aryl triflate (XV). This was coupled with the silyl sulfide intermediate (II) in the presence of CsF to produce the diaryl sulfide (XVI). After methyl ester (XVI) hydrolysis, the resultant cinnamic acid (VIII) was coupled with methyl isonipecotate (XVII) to furnish amide (XVIII). The title compound was then obtained by methyl ester (XVIII) hydrolysis with LiOH, followed by treatment with methanolic NaOH.
| 【1】 Jae, H.-S.; Pei, Z.; Staeger, M.A.; Gunawardana, I.W.; Winn, M.; Freeman, J.C.; Liu, G.; Link, J.; Boyd, S.A.; Zhu, G.-D.; Von Geldern, T.W.; Xin, Z.; Lynch, J.K.; Wang, S. (Abbott Laboratories Inc.); Cell adhesion-inhibiting antiinflammatory and immune-suppressive cpds.. WO 0059880 . |
| 【2】 Lynch, J.K.; Link, J.; Zhu, G.-D.; Boyd, S.A.; Winn, M.; Pei, Z.; Gunawardana, I.W.; Liu, G.; Xin, Z.; Jae, H.-S.; Freeman, J.C.; Von Geldern, T.; Staeger, M.A. (Abbott Laboratories Inc.); Cell adhesion-inhibiting antiinflammatory and immune-suppressive cpds.. US 6110922; WO 0039081 . |
| 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) | 53020 | 1-methyl-5-[(triisopropylsilyl)sulfanyl]-1H-indole; 1-methyl-1H-indol-5-yl triisopropylsilyl sulfide | n/a | C18H29NSSi | 详情 | 详情 |
| (VIII) | 53023 | (E)-3-{2,3-dichloro-4-[(1-methyl-1H-indol-5-yl)sulfanyl]phenyl}-2-propenoic acid | n/a | C18H13Cl2NO2S | 详情 | 详情 |
| (XI) | 53025 | 2,3-Dichlorophenol | 576-24-9 | C6H4Cl2O | 详情 | 详情 |
| (XII) | 53026 | 4-bromo-2,3-dichlorophenol | n/a | C6H3BrCl2O | 详情 | 详情 |
| (XIII) | 14156 | methyl acrylate | 96-33-3 | C4H6O2 | 详情 | 详情 |
| (XIV) | 53027 | methyl (E)-3-(2,3-dichloro-4-hydroxyphenyl)-2-propenoate | n/a | C10H8Cl2O3 | 详情 | 详情 |
| (XV) | 53028 | methyl (E)-3-(2,3-dichloro-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)-2-propenoate | n/a | C11H7Cl2F3O5S | 详情 | 详情 |
| (XVI) | 53029 | methyl (E)-3-{2,3-dichloro-4-[(1-methyl-1H-indol-5-yl)sulfanyl]phenyl}-2-propenoate | n/a | C19H15Cl2NO2S | 详情 | 详情 |
| (XVII) | 38418 | methyl 4-piperidinecarboxylate; Isonipecotic acid methyl ester; 4-piperidinecarboxylic acid methyl ester | 2971-79-1 | C7H13NO2 | 详情 | 详情 |
| (XVIII) | 53030 | methyl 1-((E)-3-{2,3-dichloro-4-[(1-methyl-1H-indol-5-yl)sulfanyl]phenyl}-2-propenoyl)-4-piperidinecarboxylate | n/a | C25H24Cl2N2O3S | 详情 | 详情 |