propyl 4-[(2R)-1,2-dihydroxybutan-2-yl]-6-methoxy-5-(phenylmethoxymethyl)pyridine-2-carboxylate | 183433-94-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: propyl 4-[(2R)-1,2-dihydroxybutan-2-yl]-6-methoxy-5-(phenylmethoxymethyl)pyridine-2-carboxylate
• CAS: 183433-94-5
• 化学式: C₂₂H₂₉NO₆
• 分子量: 403.475
• InChiKey: DTLYVEUWMPUDLW-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  98.1
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  propyl 4-[(2R)-1,2-dihydroxybutan-2-yl]-6-methoxy-5-(phenylmethoxymethyl)pyridine-2-carboxylate 在 乙酸酐 、 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 反应 16.5h， 生成 Propyl 4-but-1-en-2-yl-6-methoxy-5-(phenylmethoxymethyl)pyridine-2-carboxylate
  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：

  propyl 4-[(2R)-1-acetyloxy-2-hydroxybutan-2-yl]-6-methoxy-5-(phenylmethoxymethyl)pyridine-2-carboxylate 在 potassium tert-butylate 作用下， 以 丙醇 、 二氯甲烷 为溶剂， 以95.8 g的产率得到propyl 4-[(2R)-1,2-dihydroxybutan-2-yl]-6-methoxy-5-(phenylmethoxymethyl)pyridine-2-carboxylate
  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%.