JP2008518032A - アミノ酸n−カルボキシ無水物の合成 - Google Patents
アミノ酸n−カルボキシ無水物の合成 Download PDFInfo
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- JP2008518032A JP2008518032A JP2007539138A JP2007539138A JP2008518032A JP 2008518032 A JP2008518032 A JP 2008518032A JP 2007539138 A JP2007539138 A JP 2007539138A JP 2007539138 A JP2007539138 A JP 2007539138A JP 2008518032 A JP2008518032 A JP 2008518032A
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- C—CHEMISTRY; METALLURGY
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- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/44—Two oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
一般に、反応混合物中においては、N−カルボキシ無水物を生成することができるいずれのアミノ酸も使用してよい。例えば、そのアミノ酸は、グリシン、アラニン、バリン、ロイシン、イソロイシン、フェニルアラニン、セリン、トレオニン、リジン、Δ−ヒドロキシリジン、オルニチン、アスパラギン酸、グルタミン酸、システイン、シスチン、メチオニン、チロシン、チロキシン、プロリン、ヒドロキシプロリン、トリプトファン、又はそれらの塩もしくは誘導体であってよい。別の例として、アミノ酸の塩(硫酸塩、ハロゲン化水素酸塩、塩酸塩、又は臭化水素酸塩等)を用いて反応混合物を調製してよい。あるいは、カルボキシル基の側鎖がエステル(例えば、ベンジルエステル、p−ニトロベンジルエステル、フェニルエステル、ペンタクロロフェニルエステル、エチルエステル又はメチルエステル)で保護されているアミノ酸誘導体、又はアミノ基の側鎖がアミノ保護基で保護されているアミノ酸誘導体を用いて反応混合物を調製してもよい。そのようなアミノ保護基は、例えば、ベンジルオキシカルボニル(CBZ)、2−(4−ビフェニルイル)−2−プロピルオキシカルボニル(Bpoc)、2−ブロモベンジルオキシカルボニル、p−トルエンスルホニル、4−メトキシベンゼンスルホニル、2−クロロベンジルオキシカルボニル、2−ニトロフェニルスルホニル、4−トルエンスルホニル等からなる群から選択してよい。
ここで、図1を参照すると、アミノ酸又はその塩は、溶媒又は溶媒系の入った反応槽(又は容器)10に分散されて、反応混合物12が生成する。その反応混合物12中に第1スパージ管14及び第2スパージ管16が入れられ、それによって反応混合物12の表面下にガス及び/又は液体が導入され得る。この反応槽10には、ガスが反応槽10から出ることが可能な出口18も備わっている。その出口18には、処理装置20、好ましくは、凝縮器(又はコンデンサー)及び/又はスクラバー(又は気体洗浄装置)が接続されている。その処理装置20には、処理されたガスが処理装置20から出ることが可能な出口22がある。処理装置が凝縮器である場合の好ましい実施形態では、入口24は、凝縮されたカルボニル化試薬を反応混合物12に再導入するように配置されている。一般に、反応混合物12上面と反応槽10上部との間に若干の蒸気スペース26が存在する。百分率では、その蒸気スペース(又はガス空間)は、一般に、反応槽容量の約30%〜約40%を占めるであろう;好ましい実施形態では、その蒸気スペースは、反応槽容量の約30%を占める。
Claims (14)
- アミノ酸又はその塩、溶媒、及びカルボニル化試薬を含んで成る反応混合物を形成し(ここで、カルボニル化試薬は、ホスゲン、ジホスゲン、トリホスゲン、及びそれらの混合物からなる群から選択される)、それによって、カルボニル化試薬は、アミノ酸又はその塩と反応して、生成物としてN−カルボキシ無水物を、副生成物としてHClを生ずること
カルボニル化試薬をアミノ酸又はその塩と反応させながら反応混合物にパージガスを通すことにより、その反応混合物からHCl副生成物をパージすること、及び
パージガスは、反応混合物を通した後、その中のカルボニル化試薬を中和するために処理すること
を含んで成るN−カルボキシ無水物の製造方法。 - カルボニル化試薬はホスゲンである請求項1に記載の製造方法。
- パージガスは、窒素、ヘリウム、アルゴン、ネオン、及びそれらの混合物から成る群から選択される請求項1又は2に記載の製造方法。
- パージガスは、主に窒素である請求項1又は2に記載の製造方法。
- 溶媒は、テトラヒドロフラン、ジオキサン、ジエチルエーテル、イソプロピルエーテル、ジクロロメタン、クロロホルム、1,2−ジクロロエタン、N,N’−ジメチルホルムアミド、アセトニトリル、アセトン、酢酸エチル及びそれらの組合せから成る群から選択される請求項1〜4のいずれかに記載の製造方法。
- カルボニル化試薬は、液体の形態で反応混合物に入れられる請求項1〜5のいずれかに記載の製造方法。
- アミノ酸は、グルタミン酸のγ−ベンジルエステル、グルタミン酸のγ−エチルエステル、及びN6−CBZ−L−リジン及びそれらの塩から成る群から選択される請求項1〜6のいずれかに記載の製造方法。
- パージガスからカルボニル化試薬を凝縮させるためにパージガスを凝縮器に通すことでパージガスを処理する請求項1〜7のいずれかに記載の製造方法。
- パージガスを凝縮器に通した後、パージガス中のカルボニル化試薬を中和するスクラバーにパージガスを通すことで、更にパージガスを処理する請求項8に記載の製造方法。
- パージガス中のカルボニル化試薬を中和するスクラバーにパージガスを通すことでパージガスを処理する請求項1〜7のいずれかに記載の製造方法。
- 水酸化アンモニウム、水酸化カリウム、水酸化ナトリウム及びそれらの組み合わせから成る群から選択される塩基を用いてカルボニル化試薬を中和する請求項9又は10に記載の製造方法。
- 塩基は、水酸化ナトリウムである請求項11に記載の製造方法。
- パージガス及びカルボニル化試薬を時間をかけて加える製造方法であって、その時間の間に、モルベースで、加える平均相対速度は、各々約0.15:1〜約0.4:1の間である請求項1〜12のいずれかに記載の製造方法。
- 0.1重量%未満のHClを含むN−カルボニル無水物生成物を回収する請求項1〜13のいずれかに記載の製造方法。
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JP2021529211A (ja) * | 2018-09-28 | 2021-10-28 | ロンザ リミテッドLonza Limited | N−カルボキシ無水物の作製方法 |
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