公开(公告)号：US20100056805A1

公开(公告)日：2010-03-04

申请号：US12591081

申请日：2009-11-06

申请人： Takayuki Gotoh ,  Ichirou Araya

发明人： Takayuki Gotoh ,  Ichirou Araya

IPC分类号： C07D207/46

CPC分类号： C07D207/10 ,  C07D207/16

摘要： An industrially advantageous process for the production of (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine or an enantiomer thereof that is useful as an intermediate for the production of novel antimicrobial agents 10-(3-cyclopropylaminomethyl-4-fluoropyrrolidinyl)pyridobenzoxazine carboxylic acid derivatives.Highly stereoselective asymmetric hydrogenation of 1-protected-4-alkoxycarbonyl-3-oxopyrrolidine, followed by ester hydrolysis, followed by amidation with cyclopropylamine gives crude crystals. The crude crystals are purified by recrystallization to give a novel compound (3R,4S)-1-protected-3-cyclopropylcarbamoyl-4-hydroxypyrrolidine or an enantiomer thereof at high optical purity. The use of these intermediates enables industrial production of high-quality products of (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine or an enantiomer thereof. The process is highly simple and can produce the desired products at high purity and stable yields.

公开(公告)号：US08084622B2

公开(公告)日：2011-12-27

申请号：US12591081

申请日：2009-11-06

申请人： Takayuki Gotoh ,  Ichirou Araya

发明人： Takayuki Gotoh ,  Ichirou Araya

IPC分类号： C07D207/12

CPC分类号： C07D207/10 ,  C07D207/16

摘要： An industrially advantageous process for the production of (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine or an enantiomer thereof that is useful as an intermediate for the production of novel antimicrobial agents 10-(3-cyclopropylaminomethyl-4-fluoropyrrolidinyl)pyridobenzoxazine carboxylic acid derivatives.Highly stereoselective asymmetric hydrogenation of 1-protected-4-alkoxycarbonyl-3-oxopyrrolidine, followed by ester hydrolysis, followed by amidation with cyclopropylamine gives crude crystals. The crude crystals are purified by recrystallization to give a novel compound (3R,4S)-1-protected-3-cyclopropylcarbamoyl-4-hydroxypyrrolidine or an enantiomer thereof at high optical purity. The use of these intermediates enables industrial production of high-quality products of (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine or an enantiomer thereof. The process is highly simple and can produce the desired products at high purity and stable yields.

摘要翻译： 用于生产（3R，4S）-3-环丙基氨基甲基-4-氟吡咯烷或其对映异构体的工业上有利的方法，其可用作生产新的抗微生物剂10-（3-环丙基氨基甲基-4-氟吡咯烷基）吡啶并苯并恶嗪 羧酸衍生物。 1-保护的4-烷氧基羰基-3-氧代吡咯烷的高度立体选择性不对称氢化，然后进行酯水解，然后与环丙胺进行酰胺化，得到粗晶体。 通过重结晶纯化粗晶体，得到高光学纯度的新化合物（3R，4S）-1-保护-3-环丙基氨基甲酰基-4-羟基吡咯烷酮或其对映异构体。 这些中间体的使用使得（3R，4S）-3-环丙基氨基甲基-4-氟吡咯烷或其对映异构体的高品质产品能够工业生产。 该方法非常简单，可以以高纯度和稳定的产率生产所需产品。

公开(公告)号：US07667049B2

公开(公告)日：2010-02-23

申请号：US12224898

申请日：2007-03-08

申请人： Takayuki Gotoh ,  Ichirou Araya

发明人： Takayuki Gotoh ,  Ichirou Araya

IPC分类号： C07D207/04

CPC分类号： C07D207/10 ,  C07D207/16

摘要： An industrially advantageous process for the production of (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine or an enantiomer thereof that is useful as an intermediate for the production of novel antimicrobial agents 10-(3-cyclopropylaminomethyl-4-fluoropyrrolidinyl)pyridobenzoxazine carboxylic acid derivatives.Highly stereoselective asymmetric hydrogenation of 1-protected-4-alkoxycarbonyl-3-oxopyrrolidine, followed by ester hydrolysis, followed by amidation with cyclopropylamine gives crude crystals. The crude crystals are purified by recrystallization to give a novel compound (3R,4S)-1-protected-3-cyclopropylcarbamoyl-4-hydroxypyrrolidine or an enantiomer thereof at high optical purity. The use of these intermediates enables industrial production of high-quality products of (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine or an enantiomer thereof. The process is highly simple and can produce the desired products at high purity and stable yields.

摘要翻译： 用于生产（3R，4S）-3-环丙基氨基甲基-4-氟吡咯烷或其对映异构体的工业上有利的方法，其可用作生产新的抗微生物剂10-（3-环丙基氨基甲基-4-氟吡咯烷基）吡啶并苯并恶嗪 羧酸衍生物。 1-保护的4-烷氧基羰基-3-氧代吡咯烷的高度立体选择性不对称氢化，然后进行酯水解，然后与环丙胺进行酰胺化，得到粗晶体。 通过重结晶纯化粗晶体，得到高光学纯度的新化合物（3R，4S）-1-保护-3-环丙基氨基甲酰基-4-羟基吡咯烷酮或其对映异构体。 这些中间体的使用使得（3R，4S）-3-环丙基氨基甲基-4-氟吡咯烷或其对映异构体的高品质产品能够工业生产。 该方法非常简单，可以以高纯度和稳定的产率生产所需产品。

公开(公告)号：US20090023935A1

公开(公告)日：2009-01-22

申请号：US12224898

申请日：2007-03-08

申请人： Takayuki Gotoh ,  Ichirou Araya

发明人： Takayuki Gotoh ,  Ichirou Araya

IPC分类号： C07D207/12 ,  C07D207/09 ,  C07D207/16

CPC分类号： C07D207/10 ,  C07D207/16

摘要： An industrially advantageous process for the production of (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine or an enantiomer thereof that is useful as an intermediate for the production of novel antimicrobial agents 10-(3-cyclopropylaminomethyl-4-fluoropyrrolidinyl)pyridobenzoxazine carboxylic acid derivatives.Highly stereoselective asymmetric hydrogenation of 1-protected-4-alkoxycarbonyl-3-oxopyrrolidine, followed by ester hydrolysis, followed by amidation with cyclopropylamine gives crude crystals. The crude crystals are purified by recrystallization to give a novel compound (3R,4S)-1-protected-3-cyclopropylcarbamoyl-4-hydroxypyrrolidine or an enantiomer thereof at high optical purity. The use of these intermediates enables industrial production of high-quality products of (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine or an enantiomer thereof. The process is highly simple and can produce the desired products at high purity and stable yields.

摘要翻译： 用于生产（3R，4S）-3-环丙基氨基甲基-4-氟吡咯烷或其对映异构体的工业上有利的方法，其可用作生产新的抗微生物剂10-（3-环丙基氨基甲基-4-氟吡咯烷基）吡啶并苯并恶嗪 羧酸衍生物。 1-保护的4-烷氧基羰基-3-氧代吡咯烷的高度立体选择性不对称氢化，然后进行酯水解，然后与环丙胺进行酰胺化，得到粗晶体。 通过重结晶纯化粗晶体，得到高光学纯度的新化合物（3R，4S）-1-保护-3-环丙基氨基甲酰基-4-羟基吡咯烷酮或其对映异构体。 这些中间体的使用使得（3R，4S）-3-环丙基氨基甲基-4-氟吡咯烷或其对映异构体的高品质产品能够工业生产。 该方法非常简单，可以以高纯度和稳定的产率生产所需产品。