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：US08653295B2

公开(公告)日：2014-02-18

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： C07C69/76

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-不饱和酯可以通过在有机碱存在下使α-三氟甲基-α-羟基酯与硫酰氟（SO 2 F 2）反应来制备。 原料优选为具有作为一个β位取代基的氢原子，烷基，取代烷基，链烯基，取代烯基，芳香环基或取代芳环基作为 其他β位取代基。 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：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：US08524913B2

公开(公告)日：2013-09-03

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： C07D261/04 ,  C07C229/20

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-β-取代的β-取代的β-氨基酸可以通过使α-三氟甲基-β-取代的α，β-不饱和酯与羟胺反应以转化α-三氟甲基-β-取代的α，β-不饱和的 酯转化成α-三氟甲基-β-取代的β-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-β-取代的β-氨基酸，其中β位取代基不限于芳环或取代芳族 环组，而α位和β位的相对立体化学也可以被控制。

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：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：US08058412B2

公开(公告)日：2011-11-15

申请号：US12306826

申请日：2007-06-25

申请人： Akihiro Ishii ,  Takashi Ootsuka ,  Manabu Yasumoto ,  Hideyuki Tsuruta ,  Kenjin Inomiya ,  Koji Ueda ,  Kaori Mogi

发明人： Akihiro Ishii ,  Takashi Ootsuka ,  Manabu Yasumoto ,  Hideyuki Tsuruta ,  Kenjin Inomiya ,  Koji Ueda ,  Kaori Mogi

IPC分类号： C07D478/00 ,  C09K3/00 ,  C07C17/00 ,  C07C19/08 ,  C07C21/18

CPC分类号： C07B39/00 ,  C07B55/00 ,  C07B2200/07 ,  C07C17/16 ,  C07C67/307 ,  C07D207/16 ,  C07D209/48 ,  C07D405/04 ,  C07H19/09 ,  C07C19/08 ,  C07C69/63

摘要： There is provided a novel, useful dehydroxyfluorination agent containing sulfuryl fluoride (SO2F2) and an organic base that is free from a free hydroxyl group in the molecule. According to the present dehydroxyfluorination agent, it is not necessary to use perfluoroalkanesulfonyl fluoride, which is not preferable in large-scale use, and it is possible to advantageously produce optically-active fluoro derivatives, which are important intermediates of medicines, agricultural chemicals and optical materials, for example, 4-fluoroproline derivatives, 2′-deoxy-2′-fluorouridine derivatives, optically-active α-fluorocarboxylate derivatives, and monofluoromethyl derivatives, even in large scale.

摘要翻译： 提供了含有硫酰氟（SO 2 F 2）和分子中不含游离羟基的有机碱的新型有用的脱羟基氟化剂。 根据现有的脱羟基氟化剂，不需要使用全氟烷基磺酰氟，其在大规模使用中是不优选的，并且可以有利地制备作为药物，农药和光学的重要中间体的光学活性氟衍生物 材料，例如4-氟脯氨酸衍生物，2'-脱氧-2'-氟尿苷衍生物，光学活性α-氟代羧酸酯衍生物和单氟甲基衍生物，甚至大规模。

公开(公告)号：US20090250658A1

公开(公告)日：2009-10-08

申请号：US12306826

申请日：2007-06-25

申请人： Akihiro Ishii ,  Takashi Ootsuka ,  Manabu Yasumoto ,  Hideyuki Tsuruta ,  Kenjin Inomiya ,  Koji Ueda ,  Kaori Mogi

发明人： Akihiro Ishii ,  Takashi Ootsuka ,  Manabu Yasumoto ,  Hideyuki Tsuruta ,  Kenjin Inomiya ,  Koji Ueda ,  Kaori Mogi

IPC分类号： C09K3/00

CPC分类号： C07B39/00 ,  C07B55/00 ,  C07B2200/07 ,  C07C17/16 ,  C07C67/307 ,  C07D207/16 ,  C07D209/48 ,  C07D405/04 ,  C07H19/09 ,  C07C19/08 ,  C07C69/63

摘要： There is provided a novel, useful dehydroxyfluorination agent containing sulfuryl fluoride (SO2F2) and an organic base that is free from a free hydroxyl group in the molecule. According to the present dehydroxyfluorination agent, it is not necessary to use perfluoroalkanesulfonyl fluoride, which is not preferable in large-scale use, and it is possible to advantageously produce optically-active fluoro derivatives, which are important intermediates of medicines, agricultural chemicals and optical materials, for example, 4-fluoroproline derivatives, 2′-deoxy-2′-fluorouridine derivatives, optically-active α-fluorocarboxylate derivatives, and monofluoromethyl derivatives, even in large scale.

摘要翻译： 提供了含有硫酰氟（SO 2 F 2）和分子中不含游离羟基的有机碱的新型有用的脱羟基氟化剂。 根据现有的脱羟基氟化剂，不需要使用全氟烷基磺酰氟，其在大规模使用中是不优选的，并且可以有利地制备作为药物，农药和光学的重要中间体的光学活性氟衍生物 材料，例如4-氟脯氨酸衍生物，2'-脱氧-2'-氟尿苷衍生物，光学活性α-氟代羧酸酯衍生物和单氟甲基衍生物，甚至大规模。

公开(公告)号：US07807858B2

公开(公告)日：2010-10-05

申请号：US11795378

申请日：2006-03-17

申请人： Akihiro Ishii ,  Takashi Ootsuka ,  Manabu Yasumoto ,  Hideyuki Tsuruta ,  Kenjin Inomiya ,  Koji Ueda ,  Kaori Mogi

发明人： Akihiro Ishii ,  Takashi Ootsuka ,  Manabu Yasumoto ,  Hideyuki Tsuruta ,  Kenjin Inomiya ,  Koji Ueda ,  Kaori Mogi

IPC分类号： C07C19/08 ,  C07C205/00 ,  C07C69/63 ,  C07C51/58 ,  C07D239/02 ,  C07D207/00

CPC分类号： C07D209/48 ,  C07B39/00 ,  C07B2200/07 ,  C07C17/16 ,  C07C67/307 ,  C07D207/16 ,  C07H19/073 ,  C07C19/08 ,  C07C69/63

摘要： It was found that a fluoro derivative can be produced by reacting a hydroxy derivative with sulfuryl fluoride (SO2F2) in the presence of an organic base or in the presence of an organic base and “a salt or complex comprising an organic base and hydrogen fluoride”. According to the present production process, it is not necessary to use perfluoroalkanesulfonyl fluoride, which is not preferable in industrial use, and it is possible to advantageously produce optically-active fluoro derivatives, which are important intermediates of medicines, agricultural chemicals and optical materials, specifically 4-fluoroproline derivatives, 2′-deoxy-2′-fluorouridine derivatives, optically-active α-fluorocarboxylate derivatives, and the like, even in a large scale.

摘要翻译： 发现氟衍生物可以通过羟基衍生物与硫酰氟（SO 2 F 2）在有机碱的存在下或在有机碱和“含有机碱和氟化氢的盐或络合物”的存在下反应来制备， 。 根据本制造方法，不需要使用在工业上不优选的全氟烷基磺酰氟，可以有利地制造作为药物，农药，光学材料的重要中间体的光学活性氟衍生物， 特别是4-氟脯氨酸衍生物，2'-脱氧-2'-氟尿苷衍生物，光学活性α-氟代羧酸酯衍生物等，甚至大规模。

公开(公告)号：US20080125589A1

公开(公告)日：2008-05-29

申请号：US11795378

申请日：2006-03-17

申请人： Akihiro Ishii ,  Takashi Ootsuka ,  Manabu Yasumoto ,  Hideyuki Tsuruta ,  Kenjin Inomiya ,  Koji Ueda ,  Kaori Mogi

发明人： Akihiro Ishii ,  Takashi Ootsuka ,  Manabu Yasumoto ,  Hideyuki Tsuruta ,  Kenjin Inomiya ,  Koji Ueda ,  Kaori Mogi

IPC分类号： C07C19/08 ,  C07D207/04 ,  C07D239/54 ,  C07C69/63 ,  C07D209/32

CPC分类号： C07D209/48 ,  C07B39/00 ,  C07B2200/07 ,  C07C17/16 ,  C07C67/307 ,  C07D207/16 ,  C07H19/073 ,  C07C19/08 ,  C07C69/63

摘要： It was found that a fluoro derivative can be produced by reacting a hydroxy derivative with sulfuryl fluoride (SO2F2) in the presence of an organic base or in the presence of an organic base and “a salt or complex comprising an organic base and hydrogen fluoride”. According to the present production process, it is not necessary to use perfluoroalkanesulfonyl fluoride, which is not preferable in industrial use, and it is possible to advantageously produce optically-active fluoro derivatives, which are important intermediates of medicines, agricultural chemicals and optical materials, specifically 4-fluoroproline derivatives, 2′-deoxy-2′-fluorouridine derivatives, optically-active α-fluorocarboxylate derivatives, and the like, even in a large scale.

摘要翻译： 发现氟衍生物可以通过羟基衍生物与硫酰氟（SO 2 H 2 F 2）在有机碱的存在下或在有机碱存在下反应来制备 有机碱和“含有机碱和氟化氢的盐或络合物”。 根据本制造方法，不需要使用在工业上不优选的全氟烷基磺酰氟，可以有利地制造作为药物，农药，光学材料的重要中间体的光学活性氟衍生物， 特别是4-氟脯氨酸衍生物，2'-脱氧-2'-氟尿苷衍生物，光学活性α-氟代羧酸酯衍生物等，甚至大规模。