(2R,3S)-3-acetoxy-2-bromobutyryl chloride | 161906-03-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R,3S)-3-acetoxy-2-bromobutyryl chloride
• 英文别名: [(2S,3R)-3-bromo-4-chloro-4-oxobutan-2-yl] acetate
• CAS: 161906-03-2
• 化学式: C₆H₈BrClO₃
• 分子量: 243.485
• InChiKey: PBXAPPVHOVUTEE-WVZVXSGGSA-N

物化性质

• 沸点：
  261.0±25.0 °C(Predicted)
• 密度：
  1.586±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2R,3S)-3-acetoxy-2-bromobutyryl chloride 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲苯 、 苯 为溶剂， 反应 48.0h， 生成 dimethyl [(αS,3S)-3-(1-acetoxyethyl)-1-(4-methoxyphenyl)-4-oxoazetidin-2,2-dicarboxylate]
  参考文献：
  名称：

  Synthesis of pure methyl [(2S,3R,αR)-1-(3-bromo-4-methoxyphenyl)-3-(α-acetoxy)ethyl-4-oxoazetidin-2-carboxylate] and its enantiomer

  摘要：

  Synthesis of key intermediates leading to 2-iso-oxacephems was carried out starting from L- and D-threonine. As predicted in our previous paper (Tetrahedron Lett. 1995, 36, 8303-8306) all diastereomers of 2-iso-oxacephems can be prepared from the appropriate enantiomers of the amino acid threonine. The absolute configuration of the 2,3- and alpha -carbon atoms in the beta -lactam structure was determined by X-ray crystallographic studies. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00003-9
• 作为产物：
  描述：

  (2R,3S)-3-Acetoxy-2-bromo-butyric acid 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 以79%的产率得到(2R,3S)-3-acetoxy-2-bromobutyryl chloride
  参考文献：
  名称：

  Synthesis of pure methyl [(2S,3R,αR)-1-(3-bromo-4-methoxyphenyl)-3-(α-acetoxy)ethyl-4-oxoazetidin-2-carboxylate] and its enantiomer

  摘要：

  Synthesis of key intermediates leading to 2-iso-oxacephems was carried out starting from L- and D-threonine. As predicted in our previous paper (Tetrahedron Lett. 1995, 36, 8303-8306) all diastereomers of 2-iso-oxacephems can be prepared from the appropriate enantiomers of the amino acid threonine. The absolute configuration of the 2,3- and alpha -carbon atoms in the beta -lactam structure was determined by X-ray crystallographic studies. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00003-9

文献信息

• Asymmetric radical cyclization leading to β-lactams: Stereoselective synthesis of chiral key intermediates for carbapenem antibiotics PS-5 and thienamycin
  作者：Hiroyuki Ishibashi、Chisato Kameoka、Kazuya Kodama、Masazumi Ikeda

  DOI：10.1016/0040-4020(95)00902-7

  日期：1996.1

  A stereoselective synthesis of β-lactams by 4-exo-trig radical cyclizations of N-[2,2-bis(phenylthio)ethenyl]-α-bromo amides bearing a chiral inductor on the nitrogen atom has been examined. Bromide 8, upon treatment with Bu3SnH in the presence of AIBN in boiling benzene, gave a mixture of (4S)-2-azetidinone 12a and its (4R)-isomer 12b in a ratio of 71:29 and 69% combined yield. Similar treatment of

  已经研究了通过在氮原子上带有手性感应剂的N- [2,2-双（苯硫基）乙烯基]-α-溴酰胺的4- exo-trig自由基环化的立体选择性合成β-内酰胺的方法。溴化物8在AIBN存在下于沸腾的苯中用Bu 3 SnH处理时，得到比例为71:29和69％的（4 S）-2-氮杂环丁酮12a和（4 R）-异构体12b的混合物综合产量。用Bu 3 SnH对α-溴丁酰胺11进行类似处理，得到反式-（4 S）-2-氮杂环丁酮17a及其主要化合物（4 R）-异构体17b（70：30，77％的总收率）。在（+）-PS-5的合成中，化合物17a被转化为24，一种手性关键中间体（25）。在侧链上带有一个额外的立体生成中心[（S）-氧官能度]的溴化物28的环化以更高的（4S）-立体选择性进行，从而得到氮杂环丁酮29a作为主要产物及其（4R）-异构体29b以78:22的比例和40％的总收率。化合物29a通过氧官能度的转
• Synthesis of a chiral 1β-methylcarbapenem key intermediate using radical cyclization of N-vinylic α-bromo amides
  作者：Hiroyuki Ishibashi、Chisato Kameoka、Kazuya Kodama、Hirotaka Kawanami、Masahiro Hamada、Masazumi Ikeda

  DOI：10.1016/s0040-4020(97)00645-5

  日期：1997.7

  The chiral 1β-methylcarbapenem key intermediate 5 was synthesized by using radical cyclization of N-vinylic α-bromo amide 18 as a key step.

  通过将N-乙烯基α-溴酰胺18的自由基环化作为关键步骤，合成了手性1β-甲基卡巴培南关键中间体5。
• Synthesis of 4-oxo-2-azetidineacetic acids by means of radical cyclization of N-vinylic α-bromo amides
  作者：Hiroyuki Ishibashi、Kazuya Kodama、Chisato Kameoka、Hirotaka Kawanami、Masazumi Ikeda

  DOI：10.1016/0040-4020(96)00849-6

  日期：1996.10

  Bu3SnH-mediated radical cyclization of α-bromo amide 8, bearing phenyl and phenylthio substituents at the terminus of the N-vinylic bond, proceeded in a 4-exo-trig manner to give β-lactam 9. Ruthenium tetroxide oxidation of the phenyl group incorporated into the product 9 provided a new synthesis of 4-oxo-2-azetidineacetic acid 13, a usuful intermediate for (±)-PS-5. Chiral 4-oxo-2-azetidineacetic acids 23 and

  Bu 3 SnH介导的α-溴酰胺8的自由基环化，在N-乙烯基键的末端带有苯基和苯硫基取代基，以4 -exo-trig方式进行，得到β-内酰胺9。掺入产物9中的苯基的四氧化钌氧化提供了4-氧代-2-氮杂环丁烷乙酸13的新合成，4-氧代-2-氮杂环丁烷乙酸是（±）-PS-5的有用中间体。还通过N的不对称自由基环化获得了分别用于合成（+）-PS-5和（+）-硫霉素的关键中间体手性4-氧代-2-氮杂环丁烷乙酸23和36。-在侧链具有手性助剂的乙烯基-α-溴酰胺。
• Sulfur-Directed Regioselective Radical Cyclization Leading to .beta.-Lactams: Formal Synthesis of (.+-.)-PS-5 and (+)-Thienamycin
  作者：Hiroyuki Ishibashi、Chisato Kameoka、Hiroko Iriyama、Kazuya Kodama、Tatsunori Sato、Masazumi Ikeda

  DOI：10.1021/jo00110a035

  日期：1995.3

  A new method for the synthesis of beta-lactams by tributyltin hydride (Bu(3)SnH)-mediated radical cyclizations of N-ethenyl-alpha-bromo amides bearing sulfur-substituent(s) at the terminus of the N-vinylic bond is described. N-[2-(Phenylthio)ethenyl]-alpha-bromoacetamide (11), upon treatment with Bu(3)SnH in the presence of azobis(isobutyronitrile) (AIBN) in boiling toluene, underwent radical cyclization in a 4-exo-trig manner to give beta-lactam 13, but in low yield (22%), whereas N-[2,2-bis(phenylthio)ethenyl] congener 23 cyclized with a high degree of efficiency to give beta-lactam 25 and a partially desulfurized lactam 13 in 70% combined yield. The effectiveness of the 4-exo cyclization of 23 can be explained in terms of the high stability of the intermediate of radical 19b. Similar treatment of alpha-bromobutanamide 24 with Bu(3)SnH afforded, in 58% yield, beta-lactam 26, which was transformed, via aldehyde 31, into the key intermediate 35 for the synthesis of(+/-)-PS-5 (36). 1,2-Asymmetric induction in radical cyclizations leading to beta-lactams was then examined. Cyclization of (2S,3R)-3-acetoxy-2-bromo-N-[2-(phenylthio)ethenyl]butanamide (38) proceeded with no diastereoselectivity to give beta-lactams 40a and 40b in approximately equal amounts. However, 2,2-bis(phenylthio) congener 39 provided (3R,4R)-2-azetidinone 41a and its (3S,4S)-isomer 41b in a ratio of ca. 2:1. Similarly, (2R,3S)-butanamide 47 afforded 48a as a major product. Saponification of 48a followed by partial desulfurization of 49 gave alcohol 50, which was then subjected to Mitsunobu inversion to afford 52. This compound was converted into the key intermediate 56 for the synthesis of (+)-thienamycin (58). Reversibility of the radical cyclization leading to the beta-lactams is discussed.
• Synthesis of thienamycin-like 2-iso-oxacephems with optional stereochemistry
  作者：Zsuzsanna Sánta、József Nagy、József Nyitrai

  DOI：10.1016/j.tetasy.2006.11.034

  日期：2006.11

  All four traps-stereoisomers of 7-(1-hydroxyethyl)-2-iso-oxacephem-4-carboxylic acids, which are the 2-iso-oxacephem analogues of Thienamycin, have been synthesized. (alpha R,6R,7R)- and (alpha S,6S,7S)-7-(1-hydroxyethyl)-3-methyl-2-iso-oxacephem-4-carboxylic acids have been prepared starting from L- and D-threonine, the configuration at the a-position was inverted by using Mitsunobu reactions providing the (alpha S,6R,7R)- and (alpha R,6S,7S)-diastereomers of the compounds above. A synthetic route to the cis-annelated analogues was also worked out. (c) 2006 Elsevier Ltd. All rights reserved.