methyl (2R,4R)-2-tert-butyl-4-(hydroxymethyl)-4-methyl-1,3-oxazolidine-3-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: methyl (2R,4R)-2-tert-butyl-4-(hydroxymethyl)-4-methyl-1,3-oxazolidine-3-carboxylate
• 英文别名: methyl (2R,4R)-2-tert-butyl-4-hydroxymethyl-4-methyl-1,3-oxazolidine-3-carboxylate；methyl (2R,4R)-2-tert-butyl-4-(hydroxymethyl)-4-methyl-oxazolidine-3-carboxylate；(2R,4R)-2-t-butyl-4-hydroxymethyl-4-methyl-1,3-oxazolidine-3-carboxylic acid methyl ester
• 化学式: C₁₁H₂₁NO₄
• 分子量: 231.292
• InChiKey: VXEHBDCCFOMPDJ-LDYMZIIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (2R,4R)-2-tert-butyl-4-(hydroxymethyl)-4-methyl-1,3-oxazolidine-3-carboxylate 在 吡啶 、 palladium 10% on activated carbon 、 potassium tert-butylate 、 氢气 、 sodium hydride 、 potassium carbonate 、 对甲苯磺酸 、 对甲苯磺酰氯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 27.17h， 生成 {[(4S)-4-methyl-2-oxo-1,3-oxazolidin-4-yl]methyl}(triphenyl)phosphonium iodide
  参考文献：
  名称：

  制备α-取代的丙氨醇衍生物的手性in盐的合成

  摘要：

  本文我们报告一个手性鏻盐的合成中，{[（4-小号）-4-甲基-2-氧代-1,3-恶唑烷-4-基]甲基}（三苯基）碘化鏻13，以提供一个新的维悌希试剂用于合成α-取代的丙氨醇衍生物的一般方法。我们在此描述的方法广泛适用于与各种类型的醛反应，以提供具有高E选择性的烯烃产品，这使我们能够提供一种新的手性S1P 1激动剂合成方法，包括我们的关键中间体以及痕量胺-相关受体1（TAAR1）激动剂。

  DOI：

  10.1016/j.tet.2014.05.086
• 作为产物：
  描述：

  (2R,4S)-(-)-Dimethyl-2-(1,1-dimethylethyl)-3,4-oxazolidindicarboxylat 在 钾硼氢 、 lithium chloride 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基丙烯基脲 、 甲苯 为溶剂， 反应 3.0h， 生成 methyl (2R,4R)-2-tert-butyl-4-(hydroxymethyl)-4-methyl-1,3-oxazolidine-3-carboxylate
  参考文献：
  名称：

  Asymmetric synthesis of α,α-disubstituted α-amino alcohol derivatives

  摘要：

  Herein we report the asymmetric synthesis of alpha,alpha-disubstituted alpha-amino alcohol derivatives 22, 25 and 26, key intermediates of a novel immunomodulator, using Seebach's method. This synthetic method can be applied to the large scale synthesis of chiral sphingosine 1-phosphate-1 (S1P(1)) receptor agonists, with significant improvements to the previously reported method with regard to the reaction temperature. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2011.02.006

文献信息

• Optically Active 4,4-Di-Substituted Oxazolidine Derivative and Method for Producing Same
  申请人：Onoda Toshihiko

  公开号：US20080108828A1

  公开（公告）日：2008-05-08

  An optically active 4,4-di-substituted oxazolidine compound having the formula (I) wherein R 1 represents a substituted C 1 -C 3 alkyl group, a substituted C 2 -C 3 alkenyl group, a formyl group, a hydroxymethyl group, a group of the formula COOR, a halogenated methyl group, a phosphonium methyl group; R represents a C 1 -C 6 alkyl group, a C 2 -C 6 alkenyl group, a phenyl group or a benzyl group; R 2 represents a C 1 -C 6 alkyl group, a C 3 -C 10 cycloalkyl group, or the like or a phenyl group; R 3 represents a C 2 -C 6 alkanoyl group, a C 1 -C 6 alkyloxycarbonyl group, a benzoyl group, a phenyloxycarbonyl group or a benzyloxycarbonyl group and R 4 represents a C 1 -C 6 alkyl group or a C 2 -C 6 alkenyl group.

  具有式（I）的光学活性4,4-双取代噁唑啉化合物，其中R1代表取代的C1-C3烷基，取代的C2-C3烯基，甲酰基，羟甲基，COOR的配基，卤代甲基，磷甲基；R代表C1-C6烷基，C2-C6烯基，苯基或苄基；R2代表C1-C6烷基，C3-C10环烷基或类似物或苯基；R3代表C2-C6酰基，C1-C6烷氧羰基，苯甲酰基，苯氧羰基或苄氧羰基，R4代表C1-C6烷基或C2-C6烯基。
• OPTICALLY ACTIVE 4,4-DISUBSTITUTED OXAZOLIDINE DERIVATIVE AND METHOD FOR PRODUCING SAME
  申请人：Sankyo Company, Limited

  公开号：EP1806344A1

  公开（公告）日：2007-07-11

  [Subject] To provide optically active 4,4-di-substituted oxazolidine derivatives and procedures for their preparation. [Means to solve the subject] An optically active 4,4-di-substituted oxazolidine derivative having the general formula (I) [wherein, R1 represents a formyl group, a hydroxymethyl group, a group of formula COOR, a halogenated methyl group, a phosphonium methyl group, or the like, R represents a C1-C6 alkyl group, or the like, R2 represents a C1-C6 alkyl group, a C3-C10 cycloalkyl group, or the like, R3 represents a C2-C6 alkanoyl group, a C1-C6 alkyloxycarbonyl group, or the like, and R4 represents a C1-C6 alkyl group or a C2-C6 alkenyl group].

  主题 提供具有光学活性的 4,4-二取代噁唑烷衍生物及其制备方法。 [解决本课题的方法］ 具有通式 (I) 的光学活性的 4,4-二取代恶唑烷衍生物 其中 R1 代表甲酰基、羟甲基、式 COOR 的基团、卤代甲基、鏻甲基或类似基团、 R 代表 C1-C6 烷基或类似基团、 R2 代表 C1-C6 烷基、C3-C10 环烷基或类似基团、 R3 代表 C2-C6 烷酰基、C1-C6 烷氧羰基或类似基团，以及 R4 代表 C1-C6 烷基或 C2-C6 烯基]。
• EP1806344
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P1 agonists
  作者：Takashi Tsuji、Keisuke Suzuki、Tsuyoshi Nakamura、Taiji Goto、Yukiko Sekiguchi、Takuya Ikeda、Takeshi Fukuda、Toshiyasu Takemoto、Yumiko Mizuno、Takako Kimura、Yumi Kawase、Futoshi Nara、Takashi Kagari、Takaichi Shimozato、Chizuko Yahara、Shinichi Inaba、Tomohiro Honda、Takashi Izumi、Masakazu Tamura、Takahide Nishi

  DOI：10.1016/j.bmc.2014.05.035

  日期：2014.8

  We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particular, an ethyl group on the 2-position afforded satisfactory S1P₁/S1P₃ selectivity. These changes of the S1P₁ and S1P₃ agonistic activities caused by the alteration of substituents on the 2-position were reasonably explained by a docking study using an S1P₁ X-ray crystal structure and S1P₃ homology modeling. We found that compounds 2b and 2e had a potent in vivo immunosuppressive efficacy along with acceptable S1P₁/S1P₃ selectivity, and confirmed that these compounds had less in vivo bradycardia risk through the evaluation of heart rate change after oral administration of the compounds (30 mg/kg, p.o.) in rats.
• US7547790B2
  申请人：——

  公开号：US7547790B2

  公开（公告）日：2009-06-16