tert-butyl 3-amino-5-(trimethylsilyl)-4-pentynoate tosylate | 180676-68-0

• 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: tert-butyl 3-amino-5-(trimethylsilyl)-4-pentynoate tosylate
• 英文别名: (+/-)1,1-dimethylethyl 3-amino-5-(trimethylsilyl)-4-pentynoate, mono p-toluenesulfonic acid salt；(+/-)1,1-Dimethylethyl 3-amino-5-(trimethylsilyl)-4-pentynoate mono p-toluenesulfonic acid salt；tert-butyl 3-amino-5-trimethylsilylpent-4-ynoate;4-methylbenzenesulfonic acid
• CAS: 180676-68-0
• 化学式: C₇H₈O₃S*C₁₂H₂₃NO₂Si
• 分子量: 413.61
• InChiKey: OZTHGHIXKDVQPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.17
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-amino-5-(trimethylsilyl)-4-pentynoate tosylate 在 甲基叔丁基醚 作用下， 以 乙醇 为溶剂， 以a suitable aqueous base to give ethyl 3-amino-5-(trimethylsilyl)-4-pentynoate的产率得到ethyl 3-amino-5-(trimethylsilyl)-4-pentynoate
  参考文献：
  名称：

  Process for the preparation of ethyl

  摘要：

  本发明涉及一种新型制备乙酸乙酯3S-[[4-[[4-（氨基亚甲基）苯基]氨基]-1,4-二氧戊基]氨基]-4-戊炔酸及其药学可接受的酸加成盐的方法，包括以下步骤：将（三甲基硅基）乙炔依次与正丁基锂和4-甲醛吗啉处理，然后进行酸水解得到3-（三甲基硅基）-2-丙炔醛；将3-（三甲基硅基）-2-丙炔醛与双（三甲基硅基）胺锂处理，得到原位的N，3-双（三甲基硅基）-2-丙炔基-1-亚胺；将N，3-双（三甲基硅基）-2-丙炔基-1-亚胺与叔丁基乙酸锂处理，得到（±）1,1-二甲基乙基3-氨基-5-（三甲基硅基）-4-戊炔酸酯；将（±）1,1-二甲基乙基3-氨基-5-（三甲基硅基）-4-戊炔酸酯与对甲苯磺酸处理，得到（±）1,1-二甲基乙基3-氨基-5-（三甲基硅基）-4-戊炔酸乙酯，对甲苯磺酸盐；将得到的盐在对甲苯磺酸存在下用乙醇处理，得到（±）乙酸乙酯3-氨基-5-（三甲基硅基）-4-戊炔酸酯；将（±）乙酸乙酯3-氨基-5-（三甲基硅基）-4-戊炔酸酯脱硅得到原位的（±）乙酸乙酯3-氨基-4-戊炔酸酯；使用（R）-（-）苦杏仁酸分离（±）乙酸乙酯3-氨基-4-戊炔酸酯，并在气态盐酸存在下处理分离的产物，得到乙酸乙酯3S-氨基-4-戊炔酸酯，单盐酸盐；将乙酸乙酯3S-氨基-4-戊炔酸酯，单盐酸盐与异丁基氯甲酸酯和N-甲基吗啡碱存在下耦合到4-[[4-（氨基亚甲基）苯基]氨基]-4-氧代丁酸，单盐酸盐上，得到乙酸乙酯3S-[[4-[[4-（氨基亚甲基）苯基]氨基]-1,4-二氧戊基]氨基]-4-戊炔酸，单盐酸盐。

  公开号：

  US05536869A1

文献信息

• Kinetic Resolution of β-Amino Esters by Acylation Using Immobilized Penicillin Amidohydrolase
  作者：Bryan H. Landis、Patrick B. Mullins、Karen E. Mullins、Ping T. Wang

  DOI：10.1021/op0255130

  日期：2002.7.1

  Penicillin amidohydrolase [EC 3.5.1.11] was used to resolve stereoisomers of a beta-amino acid ester (ethyl 3-amino-5-(trimethylsilyl)-4-pentynoate) by phenylacetylation. After screening commercially available sources of the immobilized enzyme, one was found to be significantly more efficient, and this was developed at 1-L scale reaction. The effects of phenylacetic acid concentration, beta-amino acid ester concentration, and pH on bioconversion rates and side reactions were examined. The enzymatic reaction was monitored off-line by naphthoylation of samples and chiral analytical chromatography. The best conditions for the bioconversion were pH 5.7, 28 degreesC, and 14 000 units of enzyme activity per liter. The phenylacetic acid concentration was set at 50 g/L (0.37 M), and the amine at 100 g/L (0.47 M). Under these conditions, yields of the desired (S)amino acid ester were on the order of 90% with ee's of 95% or greater in less than 12 h. This process, along with a slight modification, was tested through 15 cycles at 0.4-L scale, and was scaled to 70 L. Recycle results extrapolated to approximately 25 reaction cycles before the enzyme lost 50% of its initial activity. Through three runs at 70 L, overall yield of (S)-amine was 42.7 +/- 0.6%, overall yield of (R)-phenylacetyl amide was 47.2 +/- 1.8%. The average ee of the amine (two runs) was 98.1 +/- 0.4%, for the amide the ee was 99.5 +/- 0.2%.