5-(chloromethyl)-3-(2-(2-methoxyphenoxy)ethyl)-2-oxazolidinone | 374779-58-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(chloromethyl)-3-(2-(2-methoxyphenoxy)ethyl)-2-oxazolidinone
• 英文别名: 5-chloromethyl-3-[2-(2-methoxy-phenoxy)-ethyl]-oxazolidin-2-one；5-(Chloromethyl)-3-[2-(2-methoxyphenoxy)ethyl]-1,3-oxazolidin-2-one
• CAS: 374779-58-5
• 化学式: C₁₃H₁₆ClNO₄
• 分子量: 285.727
• InChiKey: ULCZPDWUOZBMRY-UHFFFAOYSA-N

物化性质

• 沸点：
  487.8±25.0 °C(Predicted)
• 密度：
  1.243±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(chloromethyl)-3-(2-(2-methoxyphenoxy)ethyl)-2-oxazolidinone 在 sodium dithionite 、 potassium iodide sodium hydroxide 、 potassium carbonate 作用下， 以 乙醇 、 水 为溶剂， 反应 24.0h， 生成 卡维地洛
  参考文献：
  名称：

  Intermediate for the preparation of carvedilol

  摘要：

  公开号：

  EP1367052B1
• 作为产物：
  描述：

  1,3-dichloro-2-propyl-2-(2-methoxyphenoxy)ethylcarbamate(II) 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以84.66%的产率得到5-(chloromethyl)-3-(2-(2-methoxyphenoxy)ethyl)-2-oxazolidinone
  参考文献：
  名称：

  一种卡维地洛中间体5-(氯甲基)-3-(2-(2-甲氧基苯氧基)乙基)-2-恶唑烷酮的制备方法

  摘要：

  本发明公开了一种卡维地洛中间体的制备方法，包括如下步骤：(1)将化合物(II)1,3-二氯-2-丙基-2-(2-甲氧基苯氧基)乙基胺基甲酸酯、氢氧化钠和溶剂装入反应釜中，升温至反应温度，强烈搅拌反应，得反应料液；(2)反应过程中将上述反应料液泵入精馏塔中减压浓缩，塔顶回收的溶剂再回到反应釜中；(3)反应结束后，塔底浓缩液泵入结晶釜中重结晶，可得到高纯度的化合物(I)5-(氯甲基)-3-(2-(2-甲氧基苯氧基)乙基)-2-恶唑烷酮，即为所述卡维地洛中间体。本发明通过反应分离耦合技术连续地将反应产物I分离出体系外，并结晶析出，大大提高了反应原料化合物II的转化率，实现低能耗、简单、快速地连续生产，得到的反应产物I的产率大于80％，化学纯度大于98％。

  公开号：

  CN106316976A

文献信息

• Process for the preparation of carvedilol and its salts
  申请人：Kumar Ashok

  公开号：US20070027202A1

  公开（公告）日：2007-02-01

  Disclosed herein is a process for preparation of carvedilol substantially free from its bis-impurity comprises the reaction of 4-(2,3-epoxypropoxy)carbazole and 2-(2-methoxyphenoxy)ethylamine in a polar aprotic solvent media; followed by isolation of carvediol from the reaction mass as an acid addition salt and subsequent conversion into pure carvedilol.

  本文披露了一种制备基本不含其双杂质的卡维地洛的过程，包括在极性非质子溶剂介质中反应4-(2,3-环氧丙氧基)咔唑和2-(2-甲氧基苯氧基)乙胺；随后从反应混合物中分离出卡维地洛作为酸盐，并将其转化为纯卡维地洛。
• Process for the preparation of carvedilol form-ii
  申请人：Ramanjaneyulu Seeta Gorantla

  公开号：US20070055069A1

  公开（公告）日：2007-03-08

  The present invention provides a cost-effective, industrially feasible process for the manufacture of crystalline Carvedilol Form-II using novel Carvedilol salts comprising a step of reacting 4-(2,3-epoxy propoxy)carbazole (II) with 2-(2-methoxy phenoxy)ethyl amine (III) followed by acidification with mineral acid in presence of an organic solvent to yield acid addition salts, treatment of the said salts with base(s) in presence of organic solvent(s), water and isolation from the organic solvent(s) followed by crystallization from ethyl acetate.

  本发明提供了一种成本效益高、工业上可行的制备晶体卡维地洛二型的方法，使用新型卡维地洛盐，包括以下步骤：将4-(2,3-环氧丙氧基)咔唑（II）与2-(2-甲氧基苯氧基)乙基胺（III）反应，在有机溶剂存在下加入矿酸使其酸化形成酸加成盐，将所述盐在有机溶剂存在下与碱反应，加入水并从有机溶剂中分离，随后从乙酸乙酯中结晶。
• Novel process for the preparation of 1-(9h-carbazol-4-yloxy)-3-[[2-(-methoxyphenoxy)-ethyl] amino]-propan-2-ol
  申请人：Tarur Radhakrishnan Venkatasubramanian

  公开号：US20070191456A1

  公开（公告）日：2007-08-16

  The present invention discloses a novel process for preparation of carvedilol by using eco friendly solvents to obtain the said carvedilol in high purity. The said process comprises, reacting 4-hydroxy carbazole of formula (IV) with epichlorhydrin in presence of an organic solvent and a base at temperatures between 10° C.-30° C.; further reacting the resultant 4-(2,3-epoxypropoxy)- carbazole of formula (II) with a salt of 2-(2-methoxyphenoxy)ethylamine of formula (III), preferably hydrochloride salt in presence of a base and a hydroxylic solvent at temperatures between 30° C.-90° C.

  本发明揭示了一种使用环保溶剂制备卡维地洛的新工艺，以高纯度获得卡维地洛。该工艺包括，在有机溶剂和碱的存在下，将式（IV）的4-羟基咔唑与环氧氯丙烷反应，在10℃-30℃的温度下进行；进一步，在羟基溶剂的存在下，在30℃-90℃的温度下，将式（II）的4-(2,3-环氧丙氧基)-咔唑与式（III）的2-(2-甲氧基苯氧基)乙胺盐，优选为盐酸盐，在碱的存在下反应。
• PROCESS FOR THE PREPARATION OF CARVEDILOL FORM II
  申请人：RAMANJANEYULU GORANTLA SEETA

  公开号：US20090286991A1

  公开（公告）日：2009-11-19

  A cost-effective, industrially feasible process for the manufacture of crystalline Carvedilol Form-II using novel Carvedilol salts comprises the steps of reacting 4-(2,3-epoxy propoxy)carbazole (II) with 2-(2-methoxy phenoxy)ethyl amine (III) followed by acidification with mineral acid in presence of an organic solvent to yield acid addition salts, treatment of the said salts with base(s) in presence of organic solvent(s), water and isolation from the organic solvent(s) followed by crystallization from ethyl acetate.

  一种经济实惠、工业可行的制备晶体卡维地洛II型的过程，使用新型卡维地洛盐，包括以下步骤：将4-(2,3-环氧丙氧基)咔唑（II）与2-(2-甲氧基苯氧基)乙基胺（III）反应，然后在有机溶剂存在下用矿物酸酸化，得到酸加成盐，将所述盐在有机溶剂和水存在下用碱处理，从有机溶剂中分离出来，然后从乙酸乙酯中结晶。
• PROCESS FOR THE PREPARATION OF HIGHLY OPTICAL PURE CARVEDILOL
  申请人：Kim Seong-Jin

  公开号：US20090176992A1

  公开（公告）日：2009-07-09

  The present invention relates to a process for the efficient preparation of highly optical pure chiral carvedilol. According to the present invention, a chiral oxazolidin-2-one or oxazolidin-2-thione having formula 2, produced from the reaction of N-protected 2-(2-methoxyphenoxy)ethylamine with a chiral glycidol derivative is used as a key intermediate for the preparation of the chiral carvedilol. Specifically, the process for the preparation of the chiral carvedilol comprises a) reacting a compound of formula 2 with a halogenation agent, a sulfonation agent or a mitsunobu reagent to activate a hydroxyl group of the compound of formula 2, followed by nucleophilic substitution reaction with 9H-4-hydroxy carbazole to produce a compound of formula 7, and b) subjecting the obtained compound of formula 7 to a deprotection reaction in a presence of an inorganic base to produce the targeted chiral carvedilol. The process of the present invention can be accomplished in a mild condition. The process neither requires any extraordinary purification procedure, nor involves decrease of optical purity. Therefore, the process of the present invention provides highly optical pure chiral carvedilol in simple and efficient manner.

  本发明涉及一种高效制备高度光学纯手性卡维地洛的方法。根据本发明，使用由保护的N-2-(2-甲氧基苯氧基)乙基胺与手性环氧丙醇衍生物反应生成的式2手性噁唑烷-2-酮或噁唑烷-2-硫酮作为制备手性卡维地洛的关键中间体。具体而言，制备手性卡维地洛的过程包括a)将式2化合物与卤化剂、磺化剂或三宅信试剂反应以激活式2化合物的羟基，随后与9H-4-羟基咔唑进行亲核取代反应，生成式7化合物，并b)在无机碱存在下对得到的式7化合物进行去保护反应，生成目标手性卡维地洛。本发明的过程可以在温和条件下完成，既不需要任何特殊的纯化过程，也不涉及光学纯度的降低。因此，本发明的方法以简单高效的方式提供高度光学纯的手性卡维地洛。