公开(公告)号：US20140114088A1

公开(公告)日：2014-04-24

申请号：US14128362

申请日：2012-06-15

申请人： Akihiro Ishii ,  Takehisa Ishimaru ,  Takako Yamazaki ,  Manabu Yasumoto

发明人： Akihiro Ishii ,  Takehisa Ishimaru ,  Takako Yamazaki ,  Manabu Yasumoto

IPC分类号： C07C303/24

CPC分类号： C07C303/24 ,  C07C305/26

摘要： A production process of a fluorosulfuric acid aromatic-ring ester according to the present invention includes reaction of an aromatic-ring hydroxyl compound with sulfuryl fluoride (SO2F2) in the presence of a tertiary amine except pyridine and methylpyridine. The sulfuryl fluoride, used as the reactant in the production process according to the present invention, is widely adapted as a fumigant and is easily available on a large scale. Further, the target compound can be obtained rapidly with a high yield under moderate reaction conditions in the production process according to the present invention. In this way, all of the prior art problems can be solved in the production process according to the present invention. The production process according to the present invention is thus particularly useful for industrial production of the fluorosulfuric acid aromatic-ring ester.

摘要翻译： 根据本发明的氟代硫酸芳环酯的制备方法包括在除吡啶和甲基吡啶之外的叔胺存在下，芳环羟基化合物与硫酰氟（SO 2 F 2）的反应。 在根据本发明的生产方法中用作反应物的硫酰氟被广泛地用作熏蒸剂，并且容易获得大量。 此外，在本发明的制造方法中，在中等反应条件下，可以快速获得目标化合物。 以这种方式，可以在根据本发明的制造方法中解决所有现有技术问题。 因此，本发明的制造方法特别适用于氟代硫酸芳香环酯的工业化生产。

公开(公告)号：US08217196B2

公开(公告)日：2012-07-10

申请号：US12919108

申请日：2009-04-21

申请人： Akihiro Ishii ,  Takako Yamazaki ,  Manabu Yasumoto ,  Takashi Masuda ,  Hideyuki Tsuruta

发明人： Akihiro Ishii ,  Takako Yamazaki ,  Manabu Yasumoto ,  Takashi Masuda ,  Hideyuki Tsuruta

IPC分类号： C07C227/16

CPC分类号： C07C227/16 ,  C07B55/00 ,  C07C227/32 ,  C07C229/20

摘要： By reacting a β-hydroxy-α-amino acid with sulfuryl fluoride (SO2F2) in the presence of an organic base, it is possible to produce an α-fluoro-β-amino acid of the formula [2]. By using a C8-12 tertiary amine having two or more alkyl groups of C3 or higher, and especially diisopropylethylamine, as the organic base, by-production of quantery ammonium salts is effectively suppressed. By applying the production process of the present invention, it is possible to very easily produce (2R)-3-(dibenzylamino)-2-fluoropropionic acid methyl ester, which is extremely important as a pharmaceutical intermediate, with high positional selectivity even on an industrial scale.

摘要翻译： 通过在有机碱的存在下使β-羟基-α-氨基酸与硫酰氟（SO2F2）反应，可以制备式[2]的α-氟 - 二 - 氨基酸。 通过使用具有两个以上具有3个以上的烷基的C8-12叔胺，特别是二异丙基乙胺作为有机碱，有效地抑制了副铵盐的副产物。 通过应用本发明的制备方法，可以非常容易地制备作为药物中间体极其重要的（2R）-3-（二苄基氨基）-2-氟丙酸甲酯，即使在 工业规模。

公开(公告)号：US08450520B2

公开(公告)日：2013-05-28

申请号：US13266008

申请日：2010-03-23

申请人： Akihiro Ishii ,  Takako Yamazaki ,  Hideyuki Tsuruta ,  Satoru Miyazawa ,  Michitaka Ootani ,  Takashi Ootsuka ,  Mikihiro Takahashi ,  Masataka Fujimoto

发明人： Akihiro Ishii ,  Takako Yamazaki ,  Hideyuki Tsuruta ,  Satoru Miyazawa ,  Michitaka Ootani ,  Takashi Ootsuka ,  Mikihiro Takahashi ,  Masataka Fujimoto

IPC分类号： C07C67/287

CPC分类号： C07C67/317 ,  C07C69/653

摘要： According to the present invention, there is provided a production process of a 2-fluoroacrylic ester including: a bromination step of converting a 2-fluoropropionic ester to a 2-bromo-2-fluoropropionic ester by reaction of the 2-fluoropropionic ester with a nitrogen-bromine bond-containing brominating agent in the presence of a radical initiator; and a dehydrobromination step of reacting the 2-bromo-2-fluoropropionic ester with a base. It is not necessary in this process to adopt very-low-temperature conditions and to use a stoichiometric amount of expensive reagent. The target 2-fluoroacrylic ester can be thus produced at low cost.

摘要翻译： 根据本发明，提供了一种2-氟丙烯酸酯的制备方法，包括：通过2-氟代丙酸酯与2-氟丙酸酯的反应将2-氟丙酸酯转化为2-溴-2-氟丙酸酯的溴化步骤 含有溴 - 溴键的溴化剂在自由基引发剂的存在下反应; 和使2-溴-2-氟丙酸酯与碱反应的脱溴氢化步骤。 在这个过程中不需要采用非常低的温度条件和使用化学计量的昂贵的试剂。 因此可以低成本制备目标2-氟丙烯酸酯。

公开(公告)号：US20110015428A1

公开(公告)日：2011-01-20

申请号：US12919108

申请日：2009-04-21

申请人： Akihiro Ishii ,  Takako Yamazaki ,  Manabu Yasumoto ,  Takashi Masuda ,  Hideyuki Tsuruta

发明人： Akihiro Ishii ,  Takako Yamazaki ,  Manabu Yasumoto ,  Takashi Masuda ,  Hideyuki Tsuruta

IPC分类号： C07C227/16

CPC分类号： C07C227/16 ,  C07B55/00 ,  C07C227/32 ,  C07C229/20

摘要： By reacting a β-hydroxy-α-amino acid with sulfuryl fluoride (SO2F2) in the presence of an organic base, it is possible to produce an α-fluoro-β-amino acid of the formula [2]. By using a C8-12 tertiary amine having two or more alkyl groups of C3 or higher, and especially diisopropylethylamine, as the organic base, by-production of quantery ammonium salts is effectively suppressed. By applying the production process of the present invention, it is possible to very easily produce (2R)-3-(dibenzylamino)-2-fluoropropionic acid methyl ester, which is extremely important as a pharmaceutical intermediate, with high positional selectivity even on an industrial scale.

摘要翻译： 通过在有机碱的存在下使β-羟基-α-氨基酸与硫酰氟（SO2F2）反应，可以制备式[2]的α-氟 - 二 - 氨基酸。 通过使用具有两个以上具有3个以上的烷基的C8-12叔胺，特别是二异丙基乙胺作为有机碱，有效地抑制了副铵盐的副产物。 通过应用本发明的制备方法，可以非常容易地制备作为药物中间体极其重要的（2R）-3-（二苄基氨基）-2-氟丙酸甲酯，即使在 工业规模。

公开(公告)号：US09040745B2

公开(公告)日：2015-05-26

申请号：US14128362

申请日：2012-06-15

申请人： Akihiro Ishii ,  Takehisa Ishimaru ,  Takako Yamazaki ,  Manabu Yasumoto

发明人： Akihiro Ishii ,  Takehisa Ishimaru ,  Takako Yamazaki ,  Manabu Yasumoto

IPC分类号： C07C303/24

CPC分类号： C07C303/24 ,  C07C305/26

摘要： A production process of a fluorosulfuric acid aromatic-ring ester according to the present invention includes reaction of an aromatic-ring hydroxyl compound with sulfuryl fluoride (SO2F2) in the presence of a tertiary amine except pyridine and methylpyridine. The sulfuryl fluoride, used as the reactant in the production process according to the present invention, is widely adapted as a fumigant and is easily available on a large scale. Further, the target compound can be obtained rapidly with a high yield under moderate reaction conditions in the production process according to the present invention. In this way, all of the prior art problems can be solved in the production process according to the present invention. The production process according to the present invention is thus particularly useful for industrial production of the fluorosulfuric acid aromatic-ring ester.

摘要翻译： 根据本发明的氟代硫酸芳环酯的制备方法包括在除吡啶和甲基吡啶之外的叔胺存在下，芳环羟基化合物与硫酰氟（SO 2 F 2）的反应。 在根据本发明的生产方法中用作反应物的硫酰氟被广泛地用作熏蒸剂，并且容易获得大量。 此外，在本发明的制造方法中，在中等反应条件下，可以快速获得目标化合物。 以这种方式，可以在根据本发明的制造方法中解决所有现有技术问题。 因此，本发明的制造方法特别适用于氟代硫酸芳香环酯的工业化生产。

公开(公告)号：US20120059187A1

公开(公告)日：2012-03-08

申请号：US13266008

申请日：2010-03-23

申请人： Akihiro Ishii ,  Takako Yamazaki ,  Hideyuki Tsuruta ,  Satoru Miyazawa ,  Michitaka Ootani ,  Takashi Ootsuka ,  Mikihiro Takahashi ,  Masataka Fujimoto

发明人： Akihiro Ishii ,  Takako Yamazaki ,  Hideyuki Tsuruta ,  Satoru Miyazawa ,  Michitaka Ootani ,  Takashi Ootsuka ,  Mikihiro Takahashi ,  Masataka Fujimoto

IPC分类号： C07C67/307

CPC分类号： C07C67/317 ,  C07C69/653

摘要： According to the present invention, there is provided a production process of a 2-fluoroacrylic ester including: a bromination step of converting a 2-fluoropropionic ester to a 2-bromo-2-fluoropropionic ester by reaction of the 2-fluoropropionic ester with a nitrogen-bromine bond-containing brominating agent in the presence of a radical initiator; and a dehydrobromination step of reacting the 2-bromo-2-fluoropropionic ester with a base. It is not necessary in this process to adopt very-low-temperature conditions and to use a stoichiometric amount of expensive reagent. The target 2-fluoroacrylic ester can be thus produced at low cost.

摘要翻译： 根据本发明，提供了一种2-氟丙烯酸酯的制备方法，包括：通过2-氟代丙酸酯与2-氟丙酸酯的反应将2-氟丙酸酯转化为2-溴-2-氟丙酸酯的溴化步骤 含有溴 - 溴键的溴化剂在自由基引发剂的存在下反应; 和使2-溴-2-氟丙酸酯与碱反应的脱溴氢化步骤。 在这个过程中不需要采用非常低的温度条件和使用化学计量的昂贵的试剂。 因此可以低成本制备目标2-氟丙烯酸酯。

公开(公告)号：US20110152536A1

公开(公告)日：2011-06-23

申请号：US13002595

申请日：2009-08-27

申请人： Akihiro Ishii ,  Manabu Yasumoto ,  Takako Yamazaki ,  Kaori Mogi ,  Takashi Masuda

发明人： Akihiro Ishii ,  Manabu Yasumoto ,  Takako Yamazaki ,  Kaori Mogi ,  Takashi Masuda

IPC分类号： C07C229/08 ,  C07D261/02

CPC分类号： C07D261/04 ,  C07B53/00 ,  C07C229/20

摘要： α-Trifluoromethyl-β-substituted-β-amino acids can be produced by allowing α-trifluoromethyl-β-substituted-α,β-unsaturated esters to react with hydroxylamine to convert α-trifluoromethyl-β-substituted-α,β-unsaturated esters into dehydrogenated closed-ring body of α-trifluoromethyl-β-substituted-β-amino acid, and by hydrogenolyzing the dehydrogenated closed-ring body. According to this production process, novel α-trifluoromethyl-β-substituted-β-amino acids which are free amino acids whose functional groups are not protected can be produced, in which β-position substituent is not limited to aromatic ring group or substituted aromatic ring group while the relative stereochemistry of α-position and β-position can be also controlled.

摘要翻译： α-三氟甲基 - 和取代的 - 氨基酸可以通过使α-三氟甲基 - 取代的α，β-不饱和酯与羟胺反应以转化α-三氟甲基 - α，β-不饱和酯转化为α-三氟甲基 - 取代的 - 氨基酸的脱氢闭环体，并通过氢化脱氢闭环体。 根据该制造方法，可以制备作为官能团未被保护的游离氨基酸的新型α-三氟甲基 - 取代 - 取代的 - 氨基酸，其中，取代基不限于芳环基 或取代的芳族环基团，同时也可以控制相对的立体化学位置和位置。

公开(公告)号：US08426645B2

公开(公告)日：2013-04-23

申请号：US12919162

申请日：2009-01-27

申请人： Akihiro Ishii ,  Takako Yamazaki ,  Manabu Yasumoto

发明人： Akihiro Ishii ,  Takako Yamazaki ,  Manabu Yasumoto

IPC分类号： C07C257/12 ,  C07D263/04

CPC分类号： C07B53/00 ,  C07B2200/07 ,  C07C209/62 ,  C07C211/15 ,  C07C249/02 ,  C07C251/24

摘要： Disclosed is a process for producing a protected optically active fluoroamine, which comprises the step of reacting an imine-protected optically active hydroxyamine, an oxazolidine-protected optically active hydroxyamine, or a mixture of the imine-protected optically active hydroxyamine and the oxazolidine-protected optically active hydroxyamine, with sulfuryl fluoride (SO2F2) in the presence of a tertiary amine having a carbon number of 7 to 18 (produced by substituting all of three hydrogen atoms in ammonia by alkyl groups). The desired optically active fluoroamine can be produced by hydrolyzing the protected optically active fluoroamine under acidic conditions.

摘要翻译： 公开了一种制备受保护的光学活性氟胺的方法，其包括使亚胺保护的光学活性羟胺，恶唑烷保护的光学活性羟胺或亚胺保护的光学活性羟胺与恶唑烷保护的混合物 光学活性羟胺与硫酰氟（SO 2 F 2）在碳数为7〜18的叔胺（通过用氨基取代氨基中的全部三个氢原子代替烷基取代）的存在下反应。 所需的光学活性氟胺可以通过在酸性条件下水解保护的光学活性氟胺来制备。

公开(公告)号：US20110160477A1

公开(公告)日：2011-06-30

申请号：US13060565

申请日：2009-09-24

申请人： Akihiro Ishii ,  Manabu Yasumoto ,  Takako Yamazaki ,  Kaori Mogi ,  Kazunori Mori ,  Takashi Masuda

发明人： Akihiro Ishii ,  Manabu Yasumoto ,  Takako Yamazaki ,  Kaori Mogi ,  Kazunori Mori ,  Takashi Masuda

IPC分类号： C07C67/327

CPC分类号： C07C67/317 ,  C07C67/327 ,  C07C69/65

摘要： An α-trifluoromethyl-α,β-unsaturated ester can be produced by reacting an α-trifluoromethyl-α-hydroxy ester with sulfuryl fluoride (SO2F2) in the presence of an organic base. It is preferable that the raw substrate has a hydrogen atom as one β-position substituent group and either an alkyl group, a substituted alkyl group, an alkenyl group, a substituted alkenyl group, an aromatic ring group or a substituted aromatic ring group as the other β-position substituent group. It is more preferable that an ester moiety of the raw substrate is an alkyl ester. This raw substrate is readily available. Further, the desired reaction can proceed favorably with the use of this raw substrate. It is also preferable to use either 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the organic base. The desired reaction can proceed more favorably with the use of this organic base.

摘要翻译： α-三氟甲基-α，β-不饱和酯可以通过α-三氟甲基-α-羟基酯与硫酰氟（SO 2 F 2）在有机碱的存在下反应来制备。 原料优选为氢原子作为一个位置取代基和烷基，取代的烷基，链烯基，取代的烯基，芳族环基或取代的芳环基作为 另一个位置取代基。 原料的酯部更优选为烷基酯。 该原料基材容易获得。 此外，期望的反应可以有利地利用该原始基底进行。 还优选使用1,5-二氮杂双环[4.3.0]壬-5-烯（DBN）或1,8-二氮杂双环[5.4.0]十一碳-7-烯（DBU）作为有机碱。 使用该有机碱可以更有利地进行所需的反应。

公开(公告)号：US20110034732A1

公开(公告)日：2011-02-10

申请号：US12919162

申请日：2009-01-27

申请人： Akihiro Ishii ,  Takako Yamazaki ,  Manabu Yasumoto

发明人： Akihiro Ishii ,  Takako Yamazaki ,  Manabu Yasumoto

IPC分类号： C07C251/16 ,  C07C249/02 ,  C07C209/68

CPC分类号： C07B53/00 ,  C07B2200/07 ,  C07C209/62 ,  C07C211/15 ,  C07C249/02 ,  C07C251/24

摘要： Disclosed is a process for producing a protected optically active fluoroamine, which comprises the step of reacting an imine-protected optically active hydroxyamine, an oxazolidine-protected optically active hydroxyamine, or a mixture of the imine-protected optically active hydroxyamine and the oxazolidine-protected optically active hydroxyamine, with sulfuryl fluoride (SO2F2) in the presence of a tertiary amine having a carbon number of 7 to 18 (produced by substituting all of three hydrogen atoms in ammonia by alkyl groups). The desired optically active fluoroamine can be produced by hydrolyzing the protected optically active fluoroamine under acidic conditions.

摘要翻译： 公开了一种制备受保护的光学活性氟胺的方法，其包括使亚胺保护的光学活性羟胺，恶唑烷保护的光学活性羟胺或亚胺保护的光学活性羟胺与恶唑烷保护的混合物 光学活性羟胺与硫酰氟（SO 2 F 2）在碳数为7〜18的叔胺（通过用氨基取代氨基中的全部三个氢原子代替烷基取代）的存在下反应。 所需的光学活性氟胺可以通过在酸性条件下水解保护的光学活性氟胺来制备。