公开(公告)号：US07186865B2

公开(公告)日：2007-03-06

申请号：US10476650

申请日：2003-09-05

申请人： Akihiro Ishii ,  Masatomi Kanai ,  Yokusu Kuriyama ,  Manabu Yasumoto ,  Kenjin Inomiya ,  Takashi Ootsuka ,  Koji Ueda

发明人： Akihiro Ishii ,  Masatomi Kanai ,  Yokusu Kuriyama ,  Manabu Yasumoto ,  Kenjin Inomiya ,  Takashi Ootsuka ,  Koji Ueda

IPC分类号： C07C211/00

CPC分类号： C07C209/62 ,  C07B2200/07 ,  C07C211/29 ,  C07C217/58 ,  C07C249/02 ,  C07C251/24

摘要： An optically active 1-(fluoro-, trifluoromethyl- or trifluoromethoxy-substituted phenyl)alkylamine N-monoalkyl derivative represented by the formula 4 is produced by a process including (a) reacting an optically active secondary amine, represented by the formula 1, with an alkylation agent R2—X, in the presence of a base, thereby converting the secondary amine into an optically active tertiary amine represented by the formula 3; and (b) subjecting the tertiary amine to a hydrogenolysis, thereby producing the N-monoalkyl derivative, wherein R represents a fluorine atom, trifluoromethyl group or trifluoromethoxy group, n represents an integer of from 1 to 5, each of R1 and R2 independently represents an alkyl group having a carbon atom number of from 1 to 6, Me represents a methyl group, Ar represents a phenyl group or 1- or 2-naphthyl group, * represents a chiral carbon, and X represents a leaving group.

摘要翻译： 由式4表示的光学活性1-（氟 - ，三氟甲基 - 或三氟甲氧基取代的苯基）烷基胺N-单烷基衍生物通过以下方法制备，该方法包括：（a）使由式1表示的光学活性仲胺与式 烷基化剂R 2 -X在碱的存在下，由此将仲胺转化成由式3表示的光学活性叔胺; 和（b）使叔胺进行氢解，从而制备N-单烷基衍生物，其中R表示氟原子，三氟甲基或三氟甲氧基，n表示1〜5的整数，R 1 独立地表示碳原子数1〜6的烷基，Me表示甲基，Ar表示苯基或1-或2-萘基， *表示手性碳，X表示离去基团。

公开(公告)号：US20060247433A1

公开(公告)日：2006-11-02

申请号：US10552463

申请日：2004-04-09

申请人： Akihiro Ishii ,  Takashi Ootsuka ,  Masatomi Kanai ,  Yokusu Kuriyama ,  Manabu Yasumoto ,  Kenjin Inomiya ,  Koji Ueda

发明人： Akihiro Ishii ,  Takashi Ootsuka ,  Masatomi Kanai ,  Yokusu Kuriyama ,  Manabu Yasumoto ,  Kenjin Inomiya ,  Koji Ueda

IPC分类号： C07H19/12

CPC分类号： C07H19/067 ,  Y02P20/55

摘要： 1-β-D-Arabinofuranosyluracil in 3′,5′-hydroxyl-protected form is reacted with a trifluoromethanesulfonylating agent in the presence of an organic base to convert it into a 2′-triflate form, and then it is reacted with a fluorinating agent containing “a salt or complex formed by an organic base and hydrofluoric acid” to produce 2′-deoxy-2′-fluorouridine in 3′,5′-hydroxyl-protected form. A deprotecting agent is further caused to act thereon to obtain 2′-deoxy-2′-fluorouridine. The 2′-deoxy-2′-fluorouridine obtained can efficiently be purified by temporarily converting it into a 3′,5′-diacetyl form, recrystallizing the 3′,5′-diacetyl form, and then deacetylating it. Thus, high-purity 2′-deoxy-2′-fluorouridine can be produced.

摘要翻译： 3'，5'-羟基保护形式的1-β-D-阿拉伯呋喃糖尿嘧啶在有机碱的存在下与三氟甲磺酰化剂反应，将其转化为2,3-三氟甲磺酸酯形式，然后与氟化 含有“由有机碱和氢氟酸形成的盐或络合物”的试剂以产生3'，5'-羟基保护形式的2'-脱氧-2'-氟尿苷。 进一步使脱保护剂作用于其上，得到2'-脱氧-2'-氟尿苷。 所得到的2'-脱氧-2'-氟尿苷可以通过暂时转化为3'，5'-二乙酰基形式，重结晶3'，5'-二乙酰基形式，然后脱乙酰化而有效地纯化。 因此，可以制备高纯度2'-脱氧-2'-氟尿苷。

公开(公告)号：US20060128976A1

公开(公告)日：2006-06-15

申请号：US11347390

申请日：2006-02-06

申请人： Akihiro Ishii ,  Masatomi Kanai ,  Yokusu Kuriyama ,  Manabu Yasumoto ,  Kenjin Inomiya ,  Takashi Ootsuka ,  Koji Ueda

发明人： Akihiro Ishii ,  Masatomi Kanai ,  Yokusu Kuriyama ,  Manabu Yasumoto ,  Kenjin Inomiya ,  Takashi Ootsuka ,  Koji Ueda

IPC分类号： C07D317/00 ,  C07D309/00

CPC分类号： C07D317/22 ,  C07C43/315 ,  C07C45/57 ,  C07C45/59 ,  C07C45/60 ,  C07C49/84 ,  C07D317/16 ,  C07C49/80

摘要： A process for producing a brominated acetal (represented by the formula 3) includes (a) brominating a trifluoromethyl-substituted acetophenone by Br2 in the presence of an alkylene diol. It is optional to produce a trifluoromethyl-substituted 2-alkoxyacetophenone derivative (represented by the formula 9) by (b) reacting the brominated acetal with a metal alkoxide, thereby converting the brominated acetal into an ether; and (c) hydrolyzing the ether in the presence of an acid catalyst to remove an acetal group from the ether, thereby producing the 2-alkoxyacetophenone derivative. Alternatively, the 2-alkoxyacetophenone can be produced by (a) reacting a trifluoromethyl-substituted phenacyl halide with an acetalization agent, thereby converting the phenacyl halide into an acetal; (b) reacting the acetal with a metal alkoxide, thereby converting the acetal into an ether; and (c) hydrolyzing the ether in the presence of an acid catalyst to remove the acetal group from the ether.

摘要翻译： 制备溴化缩醛的方法（由式3表示）包括（a）在亚烷基二醇的存在下用Br 2 H 3溴化三氟甲基取代的苯乙酮。 （b）使溴化缩醛与金属醇盐反应，从而将溴化缩醛转化成醚，任选地制备三氟甲基取代的2-烷氧基苯乙酮衍生物（由式9表示） 和（c）在酸催化剂的存在下水解醚，以从乙醚中除去缩醛基，从而制备2-烷氧基苯乙酮衍生物。 或者，2-烷氧基苯乙酮可以通过以下方法制备：（a）使三氟甲基取代的苯甲酰甲基卤化物与缩醛化剂反应，从而将苯甲酰甲酰卤转化成缩醛; （b）使缩醛与金属醇盐反应，从而将缩醛转化成醚; 和（c）在酸催化剂存在下水解该醚，以从乙醚中除去缩醛基。

公开(公告)号：US07053248B2

公开(公告)日：2006-05-30

申请号：US10473399

申请日：2003-08-08

申请人： Akihiro Ishii ,  Masatomi Kanai ,  Yokusu Kuriyama ,  Manabu Yasumoto ,  Kenjin Inomiya ,  Takashi Ootsuka ,  Koji Ueda

发明人： Akihiro Ishii ,  Masatomi Kanai ,  Yokusu Kuriyama ,  Manabu Yasumoto ,  Kenjin Inomiya ,  Takashi Ootsuka ,  Koji Ueda

IPC分类号： C07C45/61

CPC分类号： C07D317/22 ,  C07C43/315 ,  C07C45/57 ,  C07C45/59 ,  C07C45/60 ,  C07C49/84 ,  C07D317/16 ,  C07C49/80

摘要： A process for producing a brominated acetal (represented by the formula 3) includes (a) brominating a trifluoromethyl-substituted acetophenone by Br2 in the presence of an alkylene diol. It is optional to produce a trifluoromethyl-substituted 2-alkoxyacetophenone derivative (represented by the formula 9) by (b) reacting the brominated acetal with a metal alkoxide, thereby converting the brominated acetal into an ether; and (c) hydrolyzing the ether in the presence of an acid catalyst to remove an acetal group from the ether, thereby producing the 2-alkoxyacetophenone derivative. Alternatively, the 2-alkoxyacetophenone can be produced by (a) reacting a trifluoromethyl-substituted phenacyl halide with an acetalization agent, thereby converting the phenacyl halide into an acetal; (b) reacting the acetal with a metal alkoxide, thereby converting the acetal into an ether; and (c) hydrolyzing the ether in the presence of an acid catalyst to remove the acetal group from the ether.

摘要翻译： 制备溴化缩醛的方法（由式3表示）包括（a）在亚烷基二醇的存在下用Br 2 H 3溴化三氟甲基取代的苯乙酮。 （b）使溴化缩醛与金属醇盐反应，从而将溴化缩醛转化成醚，任选地制备三氟甲基取代的2-烷氧基苯乙酮衍生物（由式9表示） 和（c）在酸催化剂的存在下水解醚，以从乙醚中除去缩醛基，从而制备2-烷氧基苯乙酮衍生物。 或者，2-烷氧基苯乙酮可以通过以下方法制备：（a）使三氟甲基取代的苯甲酰甲基卤化物与缩醛化剂反应，从而将苯甲酰甲酰卤转化成缩醛; （b）使缩醛与金属醇盐反应，从而将缩醛转化成醚; 和（c）在酸催化剂存在下水解该醚，以从乙醚中除去缩醛基。

公开(公告)号：US5905174A

公开(公告)日：1999-05-18

申请号：US60180

申请日：1998-04-15

申请人： Masatomi Kanai ,  Takashi Sakaya ,  Mineo Watanabe ,  Yoshihiko Goto ,  Ryo Nadano

发明人： Masatomi Kanai ,  Takashi Sakaya ,  Mineo Watanabe ,  Yoshihiko Goto ,  Ryo Nadano

IPC分类号： B01J27/08 ,  B01J27/125 ,  C07C45/63 ,  C07C45/82 ,  C07C45/83 ,  C07C45/00

CPC分类号： C07C45/82 ,  B01J27/08 ,  B01J27/125 ,  C07C45/63 ,  C07C45/83

摘要： The invention relates to a method for producing 3,3-dichloro-1,1,1-trifluoroacetone. This method includes a step of fluorinating pentachloroacetone by hydrogen fluoride in the presence of a fluorination catalyst. This fluorination may be conducted in a liquid phase in the presence of an antimony compound as the fluorination catalyst. Alternatively, the fluorination may be conducted in a gas phase in the presence of a fluorination catalyst which may be a fluorinated alumina or at least one compound of at least one metal selected from Al, Cr, Mn, Ni, and Co. The method is suited to an industrial scale production of 3,3-dichloro-1,1,1-trifluoroacetone. The invention further relates to another method for producing 3,3-dichloro-1,1,1-trifluoroacetone. This method includes a step of purifying a crude 3,3-dichloro-1,1,1-trifluoroacetone by a distillation in the presence of water, thereby to produce 3,3-dichloro-1,1,1-trifluoroacetone which is substantially free of organic matters other than 3,3-dichloro-1,1,1-trifluoroacetone. This crude 3,3-dichloro-1,1,1-trifluoroacetone may be the reaction products of the fluorination of pentachloroacetone in a gas phase. Due to the provision of the another method, 3,3-dichloro-1,1,1-trifluoroacetone can be produced with high yield.

摘要翻译： 本发明涉及一种生产3,3-二氯-1,1,1-三氟丙酮的方法。 该方法包括在氟化催化剂存在下用氟化氢氟化五氯丙酮的步骤。 该氟化可以在作为氟化催化剂的锑化合物的存在下在液相中进行。 或者，氟化可以在可以是氟化氧化铝或至少一种选自Al，Cr，Mn，Ni和Co的至少一种金属的化合物的氟化催化剂的存在下在气相中进行。该方法是 适合工业规模生产3,3-二氯-1,1,1-三氟丙酮。 本发明还涉及制备3,3-二氯-1,1,1-三氟丙酮的另一种方法。 该方法包括在水存在下通过蒸馏纯化粗制3,3-二氯-1,1,1-三氟丙酮的步骤，从而产生3,3-二氯-1,1,1-三氟丙酮，其基本上 不含3,3-二氯-1,1,1-三氟丙酮以外的有机物。 该粗的3,3-二氯-1,1,1-三氟丙酮可以是五氯丙酮在气相中氟化的反应产物。 由于提供另一种方法，可以高产率制备3,3-二氯-1,1,1-三氟丙酮。

公开(公告)号：US5449831A

公开(公告)日：1995-09-12

申请号：US177490

申请日：1994-01-05

申请人： Takayuki Nishimiya ,  Masatomi Kanai ,  Toshikazu Kawai

发明人： Takayuki Nishimiya ,  Masatomi Kanai ,  Toshikazu Kawai

IPC分类号： B01J23/44 ,  C07B61/00 ,  C07C17/00 ,  C07C17/12 ,  C07C17/23 ,  C07C25/13 ,  C07C205/12 ,  C07C209/36 ,  C07C211/52

CPC分类号： C07C201/08 ,  C07C17/12 ,  C07C17/23 ,  C07C209/36 ,  C07C25/13

摘要： 2-methyl-3-aminobenzo-trifluoride is prepared with high yields and high productivity by first halogenating o-trifluoromethylbenzalhalide, then secondly hydrogenating 2-trifluoromethyl-4-halogeno-benzalhalide formed by the first reaction, then thirdly nitrating 2-methyl-monohalogenobenzotrifluoride formed by the second reaction, and then fourthly hydrogenating 2-methyl-3-nitro-5-halogenobenzotrifluoride formed by the third reaction.

摘要翻译： 通过首先卤化邻 - 三氟甲基苯甲酰卤，然后第二次氢化通过第一反应形成的2-三氟甲基-4-卤代 - 亚苄基卤，然后第三次将2-甲基 - 单卤代三氟甲苯硝化，从而以高产率和高生产率制备2-甲基-3-氨基苯并三氟化硼 通过第二反应形成，然后第四次氢化由第三反应形成的2-甲基-3-硝基-5-卤代三氟甲苯。

公开(公告)号：US20070142670A1

公开(公告)日：2007-06-21

申请号：US11705089

申请日：2007-02-12

申请人： Akihiro Ishii ,  Masatomi Kanai ,  Yokusu Kuriyama ,  Manabu Yasumoto ,  Kenjin Inomiya ,  Takashi Ootsuka ,  Koji Ueda

发明人： Akihiro Ishii ,  Masatomi Kanai ,  Yokusu Kuriyama ,  Manabu Yasumoto ,  Kenjin Inomiya ,  Takashi Ootsuka ,  Koji Ueda

IPC分类号： C07C211/26

CPC分类号： C07C209/62 ,  C07B2200/07 ,  C07C211/29 ,  C07C217/58 ,  C07C249/02 ,  C07C251/24

摘要： An optically active 1-(fluoro-, trifluoromethyl- or trifluoromethoxy-substituted phenyl)alkylamine N-monoalkyl derivative represented by the formula 4 is produced by a process including (a) reacting an optically active secondary amine, represented by the formula 1, with an alkylation agent R2—X, in the presence of a base, thereby converting the secondary amine into an optically active tertiary amine represented by the formula 3; and (b) subjecting the tertiary amine to a hydrogenolysis, thereby producing the N-monoalkyl derivative, wherein R represents a fluorine atom, trifluoromethyl group or trifluoromethoxy group, n represents an integer of from 1 to 5, each of R1 and R2 independently represents an alkyl group having a carbon atom number of from 1 to 6, Me represents a methyl group, Ar represents a phenyl group or 1- or 2-naphthyl group, * represents a chiral carbon, and X represents a leaving group.

摘要翻译： 由式4表示的光学活性1-（氟 - ，三氟甲基 - 或三氟甲氧基取代的苯基）烷基胺N-单烷基衍生物通过以下方法制备，该方法包括：（a）使由式1表示的光学活性仲胺与式 烷基化剂R 2 -X在碱的存在下，由此将仲胺转化成由式3表示的光学活性叔胺; 和（b）使叔胺进行氢解，从而制备N-单烷基衍生物，其中R表示氟原子，三氟甲基或三氟甲氧基，n表示1〜5的整数，R 1 独立地表示碳原子数1〜6的烷基，Me表示甲基，Ar表示苯基或1-或2-萘基， *表示手性碳，X表示离去基团。

公开(公告)号：US20060281950A1

公开(公告)日：2006-12-14

申请号：US10560251

申请日：2004-06-08

申请人： Akihiro Ishii ,  Yokusu Kuriyama ,  Manabu Yasumoto ,  Masatomi Kanai ,  Kenjin Inomiya ,  Takashi Ootsuka ,  Koji Ueda

发明人： Akihiro Ishii ,  Yokusu Kuriyama ,  Manabu Yasumoto ,  Masatomi Kanai ,  Kenjin Inomiya ,  Takashi Ootsuka ,  Koji Ueda

IPC分类号： C07C211/02

CPC分类号： C07C209/62 ,  C07B2200/07 ,  C07C209/52 ,  C07C211/15 ,  C07C249/02 ,  C07C251/08

摘要： The present invention relates to a process for producing an optically active 1-alkyl-substituted 2,2,2-trifluoroethylamine, which is an important intermediate of medicines and agricultural chemicals, and which is represented by the formula [3] [in the formula R represents a lower alkyl group of a carbon and * represents an asymmetric carbon], or its salt by subjecting an optically active imine represented by the formula [1] to an asymmetric reduction under hydrogen atmosphere using a metal catalyst of Group VIII to convert it into an optically active secondary amine represented by the formula [2] and then by subjecting the secondary amine or its salt to hydrogenolysis. [Chem. 23]

摘要翻译： 本发明涉及一种制备光学活性的1-烷基取代的2,2,2-三氟乙基胺的方法，它是药物和农药的重要中间体，由式[3] [式 R表示碳的低级烷基，*表示不对称碳]或其盐，通过使用式（1）表示的光学活性亚胺在氢气氛下使用VIII族金属催化剂进行不对称还原，将其转化为 由式[2]表示的光学活性仲胺，然后通过使仲胺或其盐进行氢解。 [Chem。 23]

公开(公告)号：US07081551B2

公开(公告)日：2006-07-25

申请号：US10442652

申请日：2003-05-21

申请人： Akihiro Ishii ,  Manabu Yasumoto ,  Yokusu Kuriyama ,  Masatomi Kanai ,  Kanjin Inomiya

发明人： Akihiro Ishii ,  Manabu Yasumoto ,  Yokusu Kuriyama ,  Masatomi Kanai ,  Kanjin Inomiya

IPC分类号： C07C209/28 ,  C07C251/24 ,  C07C211/03

CPC分类号： C07C251/24 ,  C07C211/29

摘要： Optically active (R)-1-(4-trifluoromethylphenyl)ethylamine is a novel compound as an important intermediate for medicines and agricultural chemicals. This compound can be obtained with high optical purity and high yield by a process including the steps of (a) a dehydrocondensation of 4′-(trifluoromethyl)acetophenone and an optically active (R)-1-phenylethylamine to obtain an optically active imine; (b) asymmetrically reducing the imine into an optically active secondary amine; (c) reacting the amine with an organic acid (phthalic acid or benzenesulfonic acid), thereby obtaining a product that is a phthalate of or benzenesulfonate of the amine; (d) subjecting the product of the step (c) to a hydrogenolysis, thereby obtaining a product that is a phthalate of or benzenesuilfonate of optically active (R)-1-(4-trifluoromethylphenyl)ethylamine; and (e) neutralizing the product of the step (d) into the optically active (R)-1-(4-trifluoromethylphenyl)ethylamine.

摘要翻译： 光学活性（R）-1-（4-三氟甲基苯基）乙胺是一种新型化合物，作为药物和农药的重要中间体。 通过包括以下步骤的（a）4' - （三氟甲基）苯乙酮和光学活性（R）-1-苯基乙胺的脱氢缩合得到光学活性亚胺，可以获得具有高光学纯度和高收率的该化合物。 （b）将亚胺不对称地还原成光学活性仲胺; （c）使胺与有机酸（邻苯二甲酸或苯磺酸）反应，从而获得胺的邻苯二甲酸酯或苯磺酸盐的产物; （d）使步骤（c）的产物进行氢解，得到光学活性（R）-1-（4-三氟甲基苯基）乙胺的邻苯二甲酸酯或苯磺酸酯的产物; 和（e）将步骤（d）的产物中和到光学活性（R）-1-（4-三氟甲基苯基）乙胺中。

公开(公告)号：US06815559B2

公开(公告)日：2004-11-09

申请号：US10464838

申请日：2003-06-19

申请人： Akihiro Ishii ,  Masatomi Kanai ,  Yokusu Kuriyama ,  Manabu Yasumoto ,  Kenjin Inomiya

发明人： Akihiro Ishii ,  Masatomi Kanai ,  Yokusu Kuriyama ,  Manabu Yasumoto ,  Kenjin Inomiya

IPC分类号： C07C5300

CPC分类号： C07C51/295 ,  C07C59/115

摘要： The invention relates to a process for producing 3,3,3-trifluoro-2-hydroxypropionic acid. This process includes the step of (a) bringing a 1,1-dihalogeno-3,3,3-trifluoroacetone into contact with a basic aqueous solution. The obtained 3,3,3-trifluoro-2-hydroxypropionic acid may be reacted with a C1-C6 lower alcohol under an acidic condition, thereby producing a 3,3,3-trifluoro-2-hydroxypropionate. This propionate may be reacted with a hydride reducing agent (e.g., sodium borohydride), thereby producing 3,3,3-trifluoro-2-hydroxypropanol. These products (i.e., 3,3,3-trifluoro-2-hydroxypropionic acid and its derivatives) are important intermediates for medicines and liquid crystals.