JPH0449547B2 - - Google Patents
Info
- Publication number
- JPH0449547B2 JPH0449547B2 JP14247583A JP14247583A JPH0449547B2 JP H0449547 B2 JPH0449547 B2 JP H0449547B2 JP 14247583 A JP14247583 A JP 14247583A JP 14247583 A JP14247583 A JP 14247583A JP H0449547 B2 JPH0449547 B2 JP H0449547B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- reaction
- amino
- oxooxazolidine
- yield
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 238000006243 chemical reaction Methods 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 7
- 229910052783 alkali metal Inorganic materials 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 150000001340 alkali metals Chemical class 0.000 claims description 4
- 239000003125 aqueous solvent Substances 0.000 claims description 4
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 4
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 150000001735 carboxylic acids Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000000243 solution Substances 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- XMFFFMBLTDERID-UHFFFAOYSA-N 2-oxo-1,3-oxazolidine-4-carboxylic acid Chemical class OC(=O)C1COC(=O)N1 XMFFFMBLTDERID-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- -1 alkali metal salts Chemical class 0.000 description 6
- 239000002994 raw material Substances 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- ASBJGPTTYPEMLP-UHFFFAOYSA-N 3-chloroalanine Chemical compound ClCC(N)C(O)=O ASBJGPTTYPEMLP-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 235000008206 alpha-amino acids Nutrition 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- ORQLXCMGAMWKMJ-REOHCLBHSA-N (2r)-2-amino-3-bromopropanoic acid Chemical compound BrC[C@H](N)C(O)=O ORQLXCMGAMWKMJ-REOHCLBHSA-N 0.000 description 1
- IENJPSDBNBGIEL-DKWTVANSSA-N (2r)-2-amino-3-chloropropanoic acid;hydrochloride Chemical compound Cl.ClC[C@H](N)C(O)=O IENJPSDBNBGIEL-DKWTVANSSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- YFYASMWDAMXQQT-UHFFFAOYSA-N 2-amino-3-chlorobutanoic acid Chemical compound CC(Cl)C(N)C(O)=O YFYASMWDAMXQQT-UHFFFAOYSA-N 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 150000001371 alpha-amino acids Chemical class 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- POPBCSXDEXRDSX-DFWYDOINSA-N methyl (2r)-2-amino-3-chloropropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CCl POPBCSXDEXRDSX-DFWYDOINSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Description
【発明の詳細な説明】 本発明は一般式[Detailed description of the invention] The present invention is based on the general formula
【式】（式
中、R1，R2，R3およびR4はそれぞれ水素原子ま
たは低級アルキル基を表わす。）にて表わされる
２−オキソオキサゾリジン−４−カルボン酸類の
製造法に関し、特に、一般式
Regarding the method for producing 2-oxooxazolidine-4-carboxylic acids represented by the formula (wherein R 1 , R 2 , R 3 and R 4 each represent a hydrogen atom or a lower alkyl group), in particular, general formula
【式】（式中、Ｘはハロゲン原子
を表わし、R1，R2，R3およびR4は上記と同じ。）
にて表わされる化合物を水または水性溶媒中で、
アルカリ金属、アルカリ土類金属またはアンモニ
ウムの炭酸塩または重炭酸塩と反応させることを
特徴とする方法に関する。
本発明の上記一般式にて表わされる２−オキソ
オキサゾリジン−４−カルボン酸類はα−アミノ
酸や医薬、農薬等の合成用中間体として有用な化
合物であり、例えば、２−オキソオキサゾリジン
−４−カルボン酸を酸で加水分解すると、α−ア
ミノ酸の一種であるセリンを得ることができる。
２−オキソオキサゾリジン−４−カルボン酸類
の製造に関しては、従来、β−ヒドロキシアミノ
酸を出発物質とし、ホスゲンと反応させる方法
（日本化学雑誌、82巻1075頁（1961年））またはベ
ンジルオキシカルボニルクロリドと反応させる方
法（J.Chem.Soc1959年941頁）等が知られている
が、これらの方法は用いる試薬が危険性が高い、
高価である等必らずしも良い方法とはいえない。
本発明者らは、２−オキソオキサゾリジン−４
−カルボン酸類の工業的製造法を鋭意検討した結
果、前記一般式にて表わされるα−アミノ−β−
ハロゲノカルボン酸またはそのエステル類を原料
とし、これを水性溶媒中で炭酸塩、重炭酸塩と反
応させることにより高収率で２−オキソオキサゾ
リジン−４−カルボン酸類を製造する本発明の方
法に到達した。
本発明の方法は、従来全く知られていない新規
な製造法であり、１）安価な原料の使用で該化合
物を製造しうる、２）反応条件がゆるやかであ
り、操作が容易である、３）高収率で該化合物が
得られる等の利点を有し工業的に有用な製造方法
である。
本発明の方法で用いる、α−アミノ−β−ハロ
ゲノカルボン酸とそのエステル類についての具体
例として代表的なものを示せば、例えば、２−ア
ミノ−３−ハロゲノプロピオン酸、２−アミノ−
３−ハロゲノ酪酸、２−アミノ−３−ハロゲノ−
３−メチル酪酸、２−アミノ−３−ハロゲノペン
タン酸等とそれらのメチルエステル、エチルエス
テル、イソプロピルエステル、ｎ−ブチルエステ
ル、イソブチルエステル等である。また、ハロゲ
ン原子としては塩素または臭素が用いられる。
これらの原料は、例えば、対応するα−ハロゲ
ノアルデヒドから、α−アミノ−β−ハロゲノニ
トリルを経由して製造することが出来る。使用す
る形態としては、特に制限はなく、遊離形、鉱酸
塩また酸の場合のアルカリ金属塩、アルカリ土類
金属塩のいずれの形でも使用出来る。
一方、他の原料である炭酸塩または重炭酸塩と
してはリチウム、ナトリウム、カリウム等のアル
カリ金属塩、カルシウム、マグネシウム等のアル
カリ土類金属塩またはアンモニウム塩が用いら
れ、殊に、重炭酸塩の場合にはいずれでも良い
が、炭酸塩の場合にはアルカリ金属またはアンモ
ニウムの塩が好ましい。また、炭酸塩または重炭
酸塩を直接用いること以外にも、例えば、アルカ
リ金属、アルカリ土類金属またはアンモニウムの
水酸化物または炭酸塩の溶解液または懸濁液に二
酸化炭素ガスを吹込んだものに前記原料化合物を
添加して反応させても良い。
炭酸塩、重炭酸塩の使用量はα−アミノ−β−
ハロゲノカルボン酸類の形態により異なるが、遊
離形の場合で代表して表わすと、炭酸塩の場合
1.5〜10モル倍、重炭酸塩の場合、2.0〜10モル
倍、好ましくは両者とも３〜６モル倍である。モ
ル比が大きすぎると副反応を惹起して好ましくな
い。
反応は通常水溶液中で実施されるが、低級アル
コール類、ジオキサン、テトラヒドロフラン等の
有機溶媒と水を混合した水性溶媒中でも実施され
る。
反応温度は必ずしも厳密な制限はないが、一般
に０〜100℃、好ましくは30〜80℃の範囲であり、
反応時間は0.5〜30時間、通常1.0〜10時間の範囲
である。また、通常は常圧下に反応させるが、必
要により加圧または減圧下に反応させてもよい。
以下、本発明の方法について代表的な例を示し
更に具体的に説明するが、これらは本発明につい
ての理解を容易にするための単なる例示であり、
本発明はこれらのみに限定されないことは勿論の
こと、これらによつて何ら制限されないことは言
うまでもない。
実施例 １
重炭酸ナトリウム33.6ｇを水250mlに溶解した
液にβ−クロロアラニン12.3ｇをゆつくり加え、
60℃で1.5時間反応させる。反応液を冷却後、
6NHClでPHを4.0とする。該反応液を減圧濃縮
し、乾固させる。熱酢酸エチル100mlで６回抽出
する。抽出液を濃縮すると２−オキソオキサゾリ
ジン−４−カルボン酸の白色固体が得られた。収
量10.7ｇ（収率、81.6％）であつた。
実施例 ２
β−クロロアラニン1.85ｇを水50mlに溶解し、
重炭酸ナトリウム5.04ｇを加えて60℃で１時間反
応させる。反応液を高速液体クロマトグラフイー
にて分析したところ、収率92％で２−オキソオキ
サゾリジン−４−カルボン酸が生成していた。
実施例 ３
重炭酸ナトリウムを炭酸ナトリウム4.77ｇに代
えた以外は実施例２と同様に反応させたところ収
率84％であつた。
実施例 ４
重炭酸アンモニウム27.6ｇを、水250mlに溶解
した液にβ−ブロモアラニン16.8ｇをゆつくり加
え、50℃で２時間反応させる。反応液を高速液体
クロマトグラフイーで分析したところ、収率89％
で２オキソオキサゾリジン４−カルボン酸が生成
していた。
実施例 ５
炭酸カリウム55.3ｇを水100mlに溶かした液に
αアミノβクロロ酪酸13.7ｇをゆつくり加え、60
℃1.5時間反応させる。反応液を高速液体クロマ
トグラフイーで分析したところ、２−オキソ５−
メチルオキサゾリジン−４−カルボン酸が収率84
％で生成していた。
実施例 ６
重炭酸カリウム60ｇを水200mlに溶かした液に
β−クロロアラニンメチルエステル塩酸塩17.4ｇ
をゆつくり加え、60℃２時間反応させる。反応液
を高速液体クロマトグラフイーで分析したとこ
ろ、収率86％で２オキソオキサゾリジン４−カル
ボン酸メチルエステルが生成していた。
実施例 ７
炭酸カルシウム60ｇを水250mlに懸濁させこの
中へ二酸化炭素を吹込んで沈殿を溶解させる。こ
の溶液中にβ−クロロアラニン塩酸塩16ｇをゆつ
くり加え、50℃で2.5時間反応させる。２オキソ
オキサゾリジン４カルボン酸の収率72％であつ
た。[Formula] (In the formula, X represents a halogen atom, and R 1 , R 2 , R 3 and R 4 are the same as above.)
In water or an aqueous solvent, a compound represented by
It relates to a process characterized in that it is reacted with carbonates or bicarbonates of alkali metals, alkaline earth metals or ammonium. The 2-oxooxazolidine-4-carboxylic acids represented by the above general formula of the present invention are compounds useful as intermediates for the synthesis of α-amino acids, medicines, agricultural chemicals, etc. For example, 2-oxooxazolidine-4-carboxylic acids are When an acid is hydrolyzed with an acid, serine, which is a type of α-amino acid, can be obtained. Regarding the production of 2-oxooxazolidine-4-carboxylic acids, the conventional method is to use β-hydroxyamino acid as a starting material and react it with phosgene (Japanese Chemical Journal, Vol. 82, p. 1075 (1961)) or with benzyloxycarbonyl chloride. Reaction methods (J. Chem. Soc 1959, p. 941) are known, but these methods require the use of highly dangerous reagents.
This is not necessarily a good method as it is expensive. The present inventors have discovered that 2-oxooxazolidine-4
-As a result of intensive studies on industrial production methods of carboxylic acids, we found that α-amino-β-
Achieved the method of the present invention for producing 2-oxooxazolidine-4-carboxylic acids in high yield by using halogenocarboxylic acids or their esters as raw materials and reacting them with carbonates and bicarbonates in an aqueous solvent. did. The method of the present invention is a novel production method that has not been known in the past. 1) The compound can be produced using inexpensive raw materials. 2) The reaction conditions are mild and the operation is easy. 3. ) This is an industrially useful production method that has advantages such as the ability to obtain the compound in high yield. Representative examples of α-amino-β-halogenocarboxylic acids and esters thereof used in the method of the present invention include, for example, 2-amino-3-halogenopropionic acid, 2-amino-
3-halogenobutyric acid, 2-amino-3-halogeno-
These include 3-methylbutyric acid, 2-amino-3-halogenopentanoic acid, and their methyl esters, ethyl esters, isopropyl esters, n-butyl esters, isobutyl esters, and the like. Moreover, chlorine or bromine is used as the halogen atom. These raw materials can be produced, for example, from the corresponding α-halogenaldehyde via α-amino-β-halogenonitrile. There are no particular restrictions on the form used, and it can be used in any form, including free form, mineral acid salts, alkali metal salts in the case of acids, and alkaline earth metal salts. On the other hand, as carbonate or bicarbonate, which is another raw material, alkali metal salts such as lithium, sodium, and potassium, alkaline earth metal salts such as calcium and magnesium, or ammonium salts are used. Any salt may be used in some cases, but in the case of carbonate, alkali metal or ammonium salts are preferred. In addition to using carbonates or bicarbonates directly, for example, carbon dioxide gas may be bubbled into a solution or suspension of an alkali metal, alkaline earth metal, or ammonium hydroxide or carbonate. The above-mentioned raw material compound may be added to react. The amount of carbonate and bicarbonate used is α-amino-β-
Although it differs depending on the form of the halogenocarboxylic acid, representative examples of the free form are as follows:
1.5 to 10 times the mole, in the case of bicarbonate, 2.0 to 10 times the mole, preferably 3 to 6 times the amount for both. If the molar ratio is too large, side reactions may occur, which is undesirable. The reaction is usually carried out in an aqueous solution, but it can also be carried out in an aqueous solvent prepared by mixing water with an organic solvent such as a lower alcohol, dioxane, or tetrahydrofuran. The reaction temperature is not necessarily strictly limited, but is generally in the range of 0 to 100°C, preferably 30 to 80°C,
Reaction times range from 0.5 to 30 hours, usually from 1.0 to 10 hours. Further, although the reaction is usually carried out under normal pressure, the reaction may be carried out under increased pressure or reduced pressure if necessary. Hereinafter, typical examples of the method of the present invention will be shown and explained in more detail, but these are merely illustrative examples to facilitate understanding of the present invention.
It goes without saying that the present invention is not limited to these, and is not limited to these in any way. Example 1 12.3 g of β-chloroalanine was slowly added to a solution of 33.6 g of sodium bicarbonate dissolved in 250 ml of water.
Incubate at 60°C for 1.5 hours. After cooling the reaction solution,
Adjust the pH to 4.0 with 6NHCl. The reaction solution was concentrated under reduced pressure to dryness. Extract 6 times with 100 ml of hot ethyl acetate. When the extract was concentrated, a white solid of 2-oxooxazolidine-4-carboxylic acid was obtained. The yield was 10.7 g (yield, 81.6%). Example 2 1.85g of β-chloroalanine was dissolved in 50ml of water,
Add 5.04 g of sodium bicarbonate and react at 60°C for 1 hour. When the reaction solution was analyzed by high performance liquid chromatography, it was found that 2-oxooxazolidine-4-carboxylic acid was produced in a yield of 92%. Example 3 The reaction was carried out in the same manner as in Example 2 except that 4.77 g of sodium carbonate was used instead of sodium bicarbonate, and the yield was 84%. Example 4 16.8 g of β-bromoalanine was slowly added to a solution in which 27.6 g of ammonium bicarbonate was dissolved in 250 ml of water, and the mixture was reacted at 50° C. for 2 hours. When the reaction solution was analyzed by high performance liquid chromatography, the yield was 89%.
2oxooxazolidine 4-carboxylic acid was produced. Example 5 13.7 g of α-amino β-chlorobutyric acid was slowly added to a solution of 55.3 g of potassium carbonate dissolved in 100 ml of water.
Incubate at ℃ for 1.5 hours. When the reaction solution was analyzed by high performance liquid chromatography, it was found that 2-oxo5-
Yield of methyloxazolidine-4-carboxylic acid: 84
It was generated in %. Example 6 17.4 g of β-chloroalanine methyl ester hydrochloride was added to a solution of 60 g of potassium bicarbonate dissolved in 200 ml of water.
Slowly add and react at 60℃ for 2 hours. When the reaction solution was analyzed by high performance liquid chromatography, it was found that 2oxooxazolidine 4-carboxylic acid methyl ester was produced in a yield of 86%. Example 7 60 g of calcium carbonate is suspended in 250 ml of water and carbon dioxide is blown into the suspension to dissolve the precipitate. 16 g of β-chloroalanine hydrochloride is slowly added to this solution and reacted at 50°C for 2.5 hours. The yield of 2-oxo-oxazolidine-4-carboxylic acid was 72%.
Claims (1)
アルキル基、Ｘはハロゲン原子を表わす。）にて
表わされる化合物を水または水性溶媒中で、アル
カリ金属，アルカリ土類金属またはアンモニウム
の炭酸塩または重炭酸塩と反応させることを特徴
とする、一般式 【式】（式中、R1，R2，R3お よびR4は上記と同じ。） にて表わされる２−オキソオキサゾリジン−４−
カルボン酸類の製造法。[Scope of Claims] 1 A compound represented by the general formula [Formula] (wherein R 1 , R 2 , R 3 and R 4 each represent a hydrogen atom or a lower alkyl group, and X represents a halogen atom) characterized by reaction with carbonates or bicarbonates of alkali metals, alkaline earth metals or ammonium in water or an aqueous solvent, in which R 1 , R 2 , R 3 and R 4 is the same as above.) 2-oxooxazolidine-4-
Method for producing carboxylic acids.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14247583A JPS6034955A (en) | 1983-08-05 | 1983-08-05 | Production of 2-oxooxazolidine-4-carboxylic acids |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14247583A JPS6034955A (en) | 1983-08-05 | 1983-08-05 | Production of 2-oxooxazolidine-4-carboxylic acids |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6034955A JPS6034955A (en) | 1985-02-22 |
| JPH0449547B2 true JPH0449547B2 (en) | 1992-08-11 |
Family
ID=15316179
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14247583A Granted JPS6034955A (en) | 1983-08-05 | 1983-08-05 | Production of 2-oxooxazolidine-4-carboxylic acids |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6034955A (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE1010768A3 (en) * | 1996-11-26 | 1999-01-05 | Dsm Nv | A PROCESS FOR THE PREPARATION OF ALPHA-amino acid, alpha-amino acids and their derivatives. |
| EP1000937A4 (en) * | 1997-07-10 | 2003-02-05 | Ube Industries | Process for producing 4-alkoxycarbonyl-2-oxazolidinone compounds |
| WO2001016117A1 (en) | 1999-08-30 | 2001-03-08 | Shionogi & Co., Ltd. | Processes for the preparation of oxo-oxazoline or alloamino acid derivatives |
-
1983
- 1983-08-05 JP JP14247583A patent/JPS6034955A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6034955A (en) | 1985-02-22 |
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