6-Chloro-4-(2-ethyl-1,3-dioxolan-2-YL)-2-methoxypyridin-3-YL]methanol | 183433-66-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-Chloro-4-(2-ethyl-1,3-dioxolan-2-YL)-2-methoxypyridin-3-YL]methanol
• 英文别名: [6-chloro-4-(2-ethyl-1,3-dioxolan-2-yl)-2-methoxypyridin-3-yl]methanol
• CAS: 183433-66-1
• 化学式: C₁₂H₁₆ClNO₄
• 分子量: 273.716
• InChiKey: JQBUSZZMOSXWFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  60.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-Chloro-4-(2-ethyl-1,3-dioxolan-2-YL)-2-methoxypyridin-3-YL]methanol 在 palladium on activated charcoal palladium diacetate 、 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 sodium hypochlorite 、 四氧化锇 、 三甲基氯硅烷 、 4-acetoxy-2,2,6,6-tetramethylpiperidine-1-oxyl 、 十二/十四烷基二甲基氧化胺 、 PS-30 catalyst 、 巴拉松 、 potassium tert-butylate 、 氢气 、 碳酸氢钠 、 potassium carbonate 、 caesium carbonate 、 对甲苯磺酸 、 sodium iodide 、 potassium bromide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 、 三氟乙酸 、 叔丁醇 为溶剂， 110.0 ℃ 、103.42 kPa 条件下， 反应 235.17h， 生成 7-乙基-10-羟基喜树碱
  参考文献：
  名称：

  Practical Asymmetric Synthesis of (S)-4-Ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine- 3,6,10(4H)-trione, a Key Intermediate for the Synthesis of Irinotecan and Other Camptothecin Analogs

  摘要：

  A practical asymmetric synthesis of(S) 4-ethyl-7,8-dihydro -4-hydroxy-1H-pyrano[3, 4-f]indolizine-3,6,10(4H)-trione (1), a versatile intermediate for the synthesis of camptothecin analogs, was developed. Commercially available citrazinic acid is converted in four steps into the 2-chloro-6-methoxypyridine 5. An ortho-directed metalation followed by reaction with a formamide produces an aldehyde with the required 2,3,4,6-substituted pyridine (6) with high regioselectivity. After refunctionalization of the aldehyde, the chloropyridine is converted into an ester by a facile palladium-mediated carbonylation reaction. Wittig reaction and racemic osmylation produce the diol 16 which is resolved by an efficient lipase resolution to an ee > 99%, and a one-pot recycle of the unwanted diol enantiomer was developed. A series of high-yielding oxidation and deprotection steps convert (S)-16 into the pyridone 25, which is then converted into 1 with an ee > 99.6%.

  DOI：

  10.1021/jo970173f
• 作为产物：
  描述：

  柠嗪酸 在 sodium tetrahydroborate 、 正丁基锂 、 三甲基氯硅烷 、 POPCl₃ 、 四丁基氯化铵 、 四甲基氯化铵 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 54.5h， 生成 6-Chloro-4-(2-ethyl-1,3-dioxolan-2-YL)-2-methoxypyridin-3-YL]methanol
  参考文献：
  名称：

  Practical Asymmetric Synthesis of (S)-4-Ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine- 3,6,10(4H)-trione, a Key Intermediate for the Synthesis of Irinotecan and Other Camptothecin Analogs

  摘要：

  A practical asymmetric synthesis of(S) 4-ethyl-7,8-dihydro -4-hydroxy-1H-pyrano[3, 4-f]indolizine-3,6,10(4H)-trione (1), a versatile intermediate for the synthesis of camptothecin analogs, was developed. Commercially available citrazinic acid is converted in four steps into the 2-chloro-6-methoxypyridine 5. An ortho-directed metalation followed by reaction with a formamide produces an aldehyde with the required 2,3,4,6-substituted pyridine (6) with high regioselectivity. After refunctionalization of the aldehyde, the chloropyridine is converted into an ester by a facile palladium-mediated carbonylation reaction. Wittig reaction and racemic osmylation produce the diol 16 which is resolved by an efficient lipase resolution to an ee > 99%, and a one-pot recycle of the unwanted diol enantiomer was developed. A series of high-yielding oxidation and deprotection steps convert (S)-16 into the pyridone 25, which is then converted into 1 with an ee > 99.6%.

  DOI：

  10.1021/jo970173f

文献信息

• Practical Asymmetric Synthesis of (<i>S</i>)-4-Ethyl-7,8-dihydro-4-hydroxy-1<i>H</i>-pyrano[3,4-f]indolizine- 3,6,10(4<i>H</i>)-trione, a Key Intermediate for the Synthesis of Irinotecan and Other Camptothecin Analogs
  作者：Kevin E. Henegar、Scott W. Ashford、Ted A. Baughman、John C. Sih、Rui-Lin Gu

  DOI：10.1021/jo970173f

  日期：1997.9.1

  A practical asymmetric synthesis of(S) 4-ethyl-7,8-dihydro -4-hydroxy-1H-pyrano[3, 4-f]indolizine-3,6,10(4H)-trione (1), a versatile intermediate for the synthesis of camptothecin analogs, was developed. Commercially available citrazinic acid is converted in four steps into the 2-chloro-6-methoxypyridine 5. An ortho-directed metalation followed by reaction with a formamide produces an aldehyde with the required 2,3,4,6-substituted pyridine (6) with high regioselectivity. After refunctionalization of the aldehyde, the chloropyridine is converted into an ester by a facile palladium-mediated carbonylation reaction. Wittig reaction and racemic osmylation produce the diol 16 which is resolved by an efficient lipase resolution to an ee > 99%, and a one-pot recycle of the unwanted diol enantiomer was developed. A series of high-yielding oxidation and deprotection steps convert (S)-16 into the pyridone 25, which is then converted into 1 with an ee > 99.6%.