公开(公告)号：EP3059220A1

公开(公告)日：2016-08-24

申请号：EP13895696.6

申请日：2013-10-18

申请人： ABA Chemicals Corporation

发明人： LIN, Zhigang ,  LI, Hang ,  XU, Jun ,  QUE, Limin ,  QIN, Dongguang ,  JIANG, Yueheng

IPC分类号： C07C51/363

CPC分类号： C07C51/363 ,  C07C63/70

摘要： Provided is a method of preparing and recovering 2-methyl-5-iodobenzoic acid. The method utilizes o-methylbenzoic acid as raw material, iodinating via iodine/potassium persulfate in a mixed acid solvent to obtain a mixture of 2-methyl-5-iodobenzoic acid, 2-methyl-3-iodobenzoic acid, and 2-methyl-3, 5-diiodobenzoic acid; refining to obtain 2-methyl-5-iodobenzoic acid and recoverable mother liquor, the recoverable mother liquor being a mixture of 2-methyl-5-iodobenzoic acid, 2-methyl-3-iodobenzoic acid, and 2-methyl-3, 5-diiodobenzoic acid; conducting catalytic hydrogenation and deiodination to recover o-methylbenzoic acid and iodide ions; and oxidating the iodide ions to recover iodine. The whole process is recycled. The preparation and recovery method has cheap and easily available raw materials, and is easy of operation, has low requirements for equipment, and is suitable for large-scale industrial production.

摘要翻译： 提供了一种制备和回收2-甲基-5-碘苯甲酸的方法。 该方法以邻甲基苯甲酸为原料，通过碘/过硫酸钾在混合酸溶剂中碘化，得到2-甲基-5-碘苯甲酸，2-甲基-3-碘苯甲酸和2-甲基-3-碘苯甲酸的混合物， 3,5-二碘苯甲酸; 精制以获得2-甲基-5-碘苯甲酸和可回收母液，所述可回收母液为2-甲基-5-碘苯甲酸，2-甲基-3-碘苯甲酸和2-甲基-3,5 - 二碘苯甲酸; 进行催化氢化和脱碘以回收邻甲基苯甲酸和碘离子; 并氧化碘离子以回收碘。 整个过程被回收。 该制备和回收方法原料廉价易得，操作简单，对设备要求低，适合大规模工业化生产。

公开(公告)号：EP3115358B1

公开(公告)日：2019-09-11

申请号：EP14884887.2

申请日：2014-03-04

申请人： ABA Chemicals Corporation

发明人： LIN, Zhigang ,  XU, Jun ,  LIU, Yanqin ,  QUE, Limin ,  JIANG, Yueheng ,  CAI, Tong

IPC分类号： C07D211/42 ,  C07B53/00

公开(公告)号：EP3059220B1

公开(公告)日：2018-12-05

申请号：EP13895696.6

申请日：2013-10-18

申请人： ABA Chemicals Corporation

发明人： LIN, Zhigang ,  LI, Hang ,  XU, Jun ,  QUE, Limin ,  QIN, Dongguang ,  JIANG, Yueheng

IPC分类号： C07C51/363 ,  C07C63/70

CPC分类号： C07C51/363 ,  C07C63/70

摘要： Provided is a method of preparing and recovering 2-methyl-5-iodobenzoic acid. The method utilizes o-methylbenzoic acid as raw material, iodinating via iodine/potassium persulfate in a mixed acid solvent to obtain a mixture of 2-methyl-5-iodobenzoic acid, 2-methyl-3-iodobenzoic acid, and 2-methyl-3, 5-diiodobenzoic acid; refining to obtain 2-methyl-5-iodobenzoic acid and recoverable mother liquor, the recoverable mother liquor being a mixture of 2-methyl-5-iodobenzoic acid, 2-methyl-3-iodobenzoic acid, and 2-methyl-3, 5-diiodobenzoic acid; conducting catalytic hydrogenation and deiodination to recover o-methylbenzoic acid and iodide ions; and oxidating the iodide ions to recover iodine. The whole process is recycled. The preparation and recovery method has cheap and easily available raw materials, and is easy of operation, has low requirements for equipment, and is suitable for large-scale industrial production.

公开(公告)号：EP3170809A1

公开(公告)日：2017-05-24

申请号：EP15822780.1

申请日：2015-01-06

申请人： ABA Chemicals Corporation

发明人： LIN, Zhigang ,  JIANG, Yueheng ,  CAI, Tong

IPC分类号： C07D211/42

CPC分类号： C07D211/42

摘要： The present invention relates to a method for recycling chiral 1-benzyl-3-hydroxypiperidine by racemization, which particularly comprises using resolution-recycled chiral N-benzyl-3-hydroxypiperidine (I) as a raw material, and recycling by racemization under the effect of a strong base to obtain N-benzyl-3-hydroxypiperidine. The recycling scheme by racemization has not been reported in literature, has a simple reaction, and is suitable for mass industrial production.

摘要翻译： 本发明涉及通过外消旋再循环手性1-苄基-3-羟基哌啶的方法，其特别包括使用拆分再循环的手性N-苄基-3-羟基哌啶（I）作为原料，并通过外消旋作用 的强碱获得N-苄基-3-羟基哌啶。 外消旋回收方案尚未见文献报道，反应简单，适合大规模工业化生产。

公开(公告)号：EP3153509A1

公开(公告)日：2017-04-12

申请号：EP15803726.7

申请日：2015-01-06

申请人： ABA Chemicals Corporation

发明人： LIN, Zhigang ,  LIU, Yanqin ,  XU, Jun ,  JIANG, Yueheng ,  CAI, Tong

IPC分类号： C07D401/12

CPC分类号： C07D401/12

摘要： The Invention discloses a method for preparing a Dabigatran etexilate intermediate. The process of the method is as follows: a) taking 3-amino-4-methylamino benzoic acid as the raw material, synthesizing 2-methyl chloride-1-methyl-1H-benzimidazole-5-carboxylic acid through cyclization reaction with chloroacetyl chloride; b) the 2-methyl chloride-1-methyl-1H-benzimidazole-5-carboxylic acid generates 2-methyl chloride-1-methyl-1H-benzimidazole-5 formyl chloride under the action of oxalyl chloride; c) the 2-methyl chloride-1-methyl-1H-benzimidazole-5-formyl chloride generates N-(2-methyl chloride-1-methyl-1H-benzimidazole-5-acyl)-N-(pyridine-2-yl)-3-aminopropionic acid ethyl ester through condensation reaction with 3-(pyridine-2-yl) aminopropionic acid ethyl ester. The synthetic route has not been reported ever before; moreover, with cheap and widely available raw materials, simple unit operation and low requirement for equipment, the method is suitable for industrialized mass production.

摘要翻译： 本发明公开了一种制备达比加群酯中间体的方法。 方法工艺如下：a）以3-氨基-4-甲基氨基苯甲酸为原料，通过与氯乙酰氯进行环化反应合成2-甲基氯-1-甲基-1H-苯并咪唑-5-羧酸 ; b）2-甲基氯-1-甲基-1H-苯并咪唑-5-羧酸在草酰氯的作用下产生2-甲基氯-1-甲基-1H-苯并咪唑-5-甲酰氯; c）2-甲基氯-1-甲基-1H-苯并咪唑-5-甲酰氯生成N-（2-甲基氯-1-甲基-1H-苯并咪唑-5-酰基）-N-（吡啶-2-基 ）-3-氨基丙酸乙酯与3-（吡啶-2-基）氨基丙酸乙酯进行缩合反应。 合成路线还没有报道过; 而且采用廉价广泛的原材料，单元操作简单，设备要求低，适用于工业化批量生产。

公开(公告)号：EP3115358A1

公开(公告)日：2017-01-11

申请号：EP14884887.2

申请日：2014-03-04

申请人： ABA Chemicals Corporation

发明人： LIN, Zhigang ,  XU, Jun ,  LIU, Yanqin ,  QUE, Limin ,  JIANG, Yueheng ,  CAI, Tong

IPC分类号： C07D211/42 ,  C07B53/00

CPC分类号： C07B53/00 ,  C07D211/42

摘要： The present invention relates to a method of preparation and chiral inversion of chiral-1-t-butoxycarbonyl-3-hydroxy piperidine, the method mainly comprising the steps of: using N-benzyl-3-hydroxy piperidine as raw material, and splitting to obtain (S) or (R)-1-benzyl-3-hydroxy piperidine camsylate; dissociating by a base to obtain (S) or (R)-1-benzyl-3-hydroxy piperidine; conducting hydrogenating debenzylation/t-butoxycarbonyl protection by palladium-charcoal to obtain (S) or (R)-1-t-butoxycarbonyl-3-hydroxy piperidine. Using (R) or (S)-1-substituted-3-hydroxy piperidine as raw material, and acylating the substituted sulfonyl chloride to obtain (R) or (S)-1-substituted-3-hydroxy piperidine sulfonic ester; substituting in substitute carboxylates to obtain (S) or (R)-1-substituted-3-hydroxy piperidine carboxylic ester; hydrolyzing by base to obtain (S) or (R)-1-substituted-3-hydroxy piperidine. The synthesis route has mild reaction conditions, and is suitable for industrial mass production.

摘要翻译： 本发明涉及手性1-叔丁氧基羰基-3-羟基哌啶的制备和手性反转的方法，该方法主要包括以N-苄基-3-羟基哌啶为原料，分解为 得到（S）或（R）-1-苄基-3-羟基哌啶樟脑磺酸盐; 用碱解离得到（S）或（R）-1-苄基-3-羟基哌啶; 通过钯炭进行氢化脱苄基化/叔丁氧羰基保护，得到（S）或（R）-1-叔丁氧基羰基-3-羟基哌啶。 使用（R）或（S）-1-取代-3-羟基哌啶作为原料，并酰化取代的磺酰氯，得到（R）或（S）-1-取代-3-羟基哌啶磺酸酯; 用替代羧酸酯代替（S）或（R）-1-取代-3-羟基哌啶羧酸酯; 用碱水解，得到（S）或（R）-1-取代-3-羟基哌啶。 合成路线具有温和的反应条件，适用于工业批量生产。

公开(公告)号：EP2889292B1

公开(公告)日：2020-03-25

申请号：EP12883391.0

申请日：2012-08-24

申请人： ABA Chemicals Corporation

发明人： JIANG, Yueheng ,  QUE, Limin ,  CAI, Tong ,  QIN, Dongguang

IPC分类号： C07D249/04 ,  C07D405/04 ,  C07D405/06

公开(公告)号：EP3153498B1

公开(公告)日：2019-08-21

申请号：EP15803170.8

申请日：2015-01-06

申请人： ABA Chemicals Corporation

发明人： LIN, Zhigang ,  LIU, Yanqin ,  XU, Jun ,  JIANG, Yueheng ,  CAI, Tong

IPC分类号： C07C255/58 ,  C07C253/30 ,  C07D271/07

公开(公告)号：EP3153498A1

公开(公告)日：2017-04-12

申请号：EP15803170.8

申请日：2015-01-06

申请人： ABA Chemicals Corporation

发明人： LIN, Zhigang ,  LIU, Yanqin ,  XU, Jun ,  JIANG, Yueheng ,  CAI, Tong

IPC分类号： C07C255/58 ,  C07C253/30 ,  C07D271/07

CPC分类号： C07C253/30 ,  C07C255/58 ,  C07D271/07

摘要： Disclosed is an N-substituted phenyl glycine (dabigatran etexilate intermediate) preparation method unreported in any document, the method comprising: utilizing cheap and easily available substituted aniline (1) as raw material to condense with glyoxylic acid to form an imine, while conducting hydrogenation reduction to obtain N-(substituted phenyl) glycine. The synthetic route is not reported in any document, and the raw material is cheap and easily available; in addition, the present invention has simple unit operation and low device requirement, and is suitable for large-scale industrial production.

摘要翻译： 公开了任何文献中没有报道的N-取代苯基甘氨酸（达比加群酯中间体）的制备方法，该方法包括：使用便宜且容易获得的取代苯胺（1）作为原料与乙醛酸缩合形成亚胺，同时进行氢化 还原得到N-（取代苯基）甘氨酸。 合成路线不在任何文件中报道，原材料便宜且易于获得; 另外本发明的单元操作简单，装置要求低，适用于大规模的工业化生产。

公开(公告)号：EP2889292A1

公开(公告)日：2015-07-01

申请号：EP12883391.0

申请日：2012-08-24

申请人： ABA Chemicals Corporation

发明人： JIANG, Yueheng ,  QUE, Limin ,  CAI, Tong ,  QIN, Dongguang

IPC分类号： C07D249/04 ,  C07D405/04 ,  C07D405/06

CPC分类号： C07D249/04 ,  C07D405/04 ,  C07D405/06

摘要： Disclosed is a 2-substituted-2H-1,2,3-triazole derivative, a compound as represented by formula I or II. Also disclosed is a preparation method of the compound as represented by formula I or II, in particular to a preparation method of 2-substituted-4-bromo-5-chloro-1H-1,2,3-triazole, 2-substituted-4-bromo-5-iodo-1H-1,2,3-triazole, and 2-substituted-5-chloro-1H-1,2,3-triazole-4-carboxylic acid. The preparation methods of the present invention are simple and feasible, and has high yield of the obtained compounds.

摘要翻译： 公开了2-取代-2H-1,2,3-三唑衍生物，由式I或II表示的化合物。 还公开了式I或II表示的化合物的制备方法，特别是2-取代-4-溴-5-氯-1H-1,2,3-三唑的制备方法，2-取代的 4-溴-5-碘-1H-1,2,3-三唑和2-取代-5-氯-1H-1,2,3-三唑-4-羧酸。 本发明的制备方法简单可行，得到的化合物的收率高。