JPS5944301B2 - β-fluoroaspartic acid and its production method - Google Patents
β-fluoroaspartic acid and its production methodInfo
- Publication number
- JPS5944301B2 JPS5944301B2 JP14573476A JP14573476A JPS5944301B2 JP S5944301 B2 JPS5944301 B2 JP S5944301B2 JP 14573476 A JP14573476 A JP 14573476A JP 14573476 A JP14573476 A JP 14573476A JP S5944301 B2 JPS5944301 B2 JP S5944301B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- fluoroaspartic
- diaminosuccinic
- hydrogen fluoride
- nitrite
- 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
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明は新規なβ−フルオロアスパラギン酸およびその
製法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel β-fluoroaspartic acid and a method for producing the same.
本発明の目的化合物β−フルオロアスパラギン酸は５−
フルオロウラシル、フトラフール等の医薬の合成中間体
として有用な化合物である。The object compound of the present invention β-fluoroaspartic acid is 5-
It is a compound useful as a synthetic intermediate for pharmaceuticals such as fluorouracil and ftorafur.
本発明によれば、目的とするβ−フルオロアスパラギン
酸は下記反応式で示される如く、ジアミノコハク酸と亜
硝酸塩およびフッ化水素もしくはフッ化ホウ素酸とを反
応させることにより製することが出来る。ＨＯＣＯ−Ｃ
Ｈ−ＣＨ−ＣＯＯＨ
ＮＨ２ＮＨ２
〔■〕
↓ ＨＦまたはＨＢＦ４＋ＮＯ２′
ＨＯＣＯ−ＣＨ−ＣＨ−ＣＯＯＨ
〔Ｉ〕
本発明の反応は、例えば水、ピリジン等の適当な溶媒中
もしくは非溶媒中ジアミノコハク酸〔１に亜硝酸塩およ
びフッ化水素を作用させるか、あるいは水溶液中ジアミ
ノコハク酸に亜硝酸塩およびフッ化ホウ素酸を作用させ
て実施するのが好ましい。According to the present invention, the target β-fluoroaspartic acid can be produced by reacting diaminosuccinic acid, nitrite, and hydrogen fluoride or fluoroboric acid, as shown in the reaction formula below. HOCO-C
H-CH-COOH NH2NH2 [■] ↓ HF or HBF4+NO2' HOCO-CH-CH-COOH [I] The reaction of the present invention is carried out by reacting diaminosuccinic acid [1] in a suitable solvent such as water or pyridine or in a non-solvent. Preferably, the reaction is carried out by reacting nitrite and hydrogen fluoride, or by reacting diaminosuccinic acid in an aqueous solution with nitrite and fluoroboric acid.
亜硝酸塩としては、例えば亜硝酸サトリウム、亜硝酸バ
リウム等のジアゾ化試薬が好適に用いられる。反応はい
ずれの場合にも冷却乃至加温、とりわけ−４０〜−２０
℃附近にて好適に進行する。かくして生成した目的化合
物〔Ｉ〕は、例えば反応終了液を濃縮し得られる残査に
つきイオン交換樹脂処理、等電点晶析法等の通常のアミ
ノ酸単離精製法に付すことにより容易に単離することが
出来る。本発明の目的化合物〔Ｉ〕は、例えば下記反応
式で示される如くして５−フルオロウラシルに誘導する
ことが出来る。As the nitrite, diazotizing reagents such as sodium nitrite and barium nitrite are preferably used. In either case, the reaction is carried out by cooling or heating, especially from -40 to -20
It progresses suitably around ℃. The target compound [I] thus produced can be easily isolated, for example, by concentrating the reaction-completed liquid and subjecting the resulting residue to a conventional amino acid isolation and purification method such as ion exchange resin treatment or isoelectric focusing crystallization. You can. The object compound [I] of the present invention can be derived into 5-fluorouracil, for example, as shown in the following reaction formula.
実施例 １
７０％フツ化水素−ピリジン溶液にジアミノコハク酸７
．４９（０．０５モル）を溶解し、外浴温度一１０〜−
５℃で激しくかくはんしながら亜硝酸サトリウム４．９
ｇ（０，０７モル）を徐々に加える。Example 1 Diaminosuccinic acid 7 in 70% hydrogen fluoride-pyridine solution
．． 49 (0.05 mol) and the outer bath temperature was -10 to -
Sodium nitrite 4.9 with vigorous stirring at 5℃
g (0.07 mol) are gradually added.
添加したのち同温度で２時間かくはんする。反応終了液
より溶媒を留去し得られる残査に飽和重曹水を加えＰＨ
２〜３に調整する。不溶物を口去し、口液に塩酸１０ｍ
１を加えたのち減圧濃縮する。得られる残査をメタノー
ル２００ｍ１にて抽出し、抽出液より不溶物を口去する
。口液に濃アンモニア水を加えＰＨ４．Ｏに調整する。
析出する結晶を口取し小量の水に溶解するこの溶液をイ
オン交換樹脂アンバーライトＩＲ−１２０（Ｈ＋型）（
３００ｍ１）カラムに導通する。水洗したのちこのカラ
ムに２％塩酸を流して溶出し、溶出液を濃縮して出来る
だけ塩酸を留去する。得られる残査を少量の水に溶解し
、濃アンモニア水でＰＨ３〜４に調整する。析出する結
晶を口取し、メタノールで洗浄することにより、β−フ
ルオロアスパラギン酸２．９ｇを得る。収率３８％。実
施例 ２
ジアミノコハク酸１４８９（０，１モル）をフツ化水素
５０ｍ１に外浴温度−５０〜−３０℃にて溶解し、これ
にかくはんしながら亜硝酸サトリウム９．３９（０．１
５モル）を徐々に加える。After addition, stir at the same temperature for 2 hours. The solvent was distilled off from the reaction completed solution, and saturated sodium bicarbonate solution was added to the resulting residue to adjust the pH.
Adjust to 2-3. Remove the insoluble matter and add 10 m of hydrochloric acid to the oral fluid.
After adding 1, it is concentrated under reduced pressure. The resulting residue was extracted with 200 ml of methanol, and the insoluble matter was removed from the extract. Add concentrated ammonia water to the oral fluid and adjust the pH to 4. Adjust to O.
Take the precipitated crystals, dissolve them in a small amount of water, and add this solution to the ion exchange resin Amberlite IR-120 (H+ type) (
300ml) column. After washing with water, the column is eluted with 2% hydrochloric acid, and the eluate is concentrated to remove as much of the hydrochloric acid as possible. The resulting residue is dissolved in a small amount of water, and the pH is adjusted to 3-4 with concentrated ammonia water. By taking the precipitated crystals and washing them with methanol, 2.9 g of β-fluoroaspartic acid is obtained. Yield 38%. Example 2 Diaminosuccinic acid 1489 (0.1 mol) was dissolved in 50 ml of hydrogen fluoride at an external bath temperature of -50 to -30°C, and while stirring, 9.39 (0.1 mol) of sodium nitrite was dissolved in 50 ml of hydrogen fluoride.
5 mol) gradually.
以下実施例１と同様に処理することにより、β−フルオ
ロアスパラギン酸７．８９を得る。収率５２％ｏ本品の
物理化学的性状は実施例１で得られた標品のそれに一致
した。実施例 ３
ジアミノコハク酸１４．８９（０．１モル）を４２％フ
ツ化ホウ酸水溶液７０ｍ１に溶解し、これに激しくかく
はんしながら亜硝酸サトリウム９３９を含む水２０ｍ１
溶液をＯ〜５゜Ｃにて徐々に加える。Thereafter, by processing in the same manner as in Example 1, 7.89 g of β-fluoroaspartic acid was obtained. Yield: 52% o The physicochemical properties of this product matched those of the standard product obtained in Example 1. Example 3 14.89 (0.1 mol) of diaminosuccinic acid was dissolved in 70 ml of a 42% fluoroboric acid aqueous solution, and while stirring vigorously, 20 ml of water containing sodium nitrite 939 was added.
Add the solution slowly at 0-5°C.
Claims (1)
くはフッ化ホウ素酸とを反応させることを特徴とするβ
−フルオロアスパラギン酸の製法。 ３ ジアミノコハク酸と亜硝酸ナトリウムおよびフッ化
水素とをピリジン溶媒中で冷却下に反応させる特許請求
の範囲第２項記載の製法。 ４ ジアミノコハク酸と亜硝酸ナトリウムおよびフッ化
水素とを冷却下に反応させる特許請求の範囲第２項記載
の製法。 ５ ジアミノコハク酸と亜硝酸ナトリウムおよびフッ化
ホウ素酸とを水溶液中冷却下に反応させる特許請求の範
囲第２項記載の製法。[Claims] 1 β-fluoroaspartic acid. 2 β characterized by reacting diaminosuccinic acid with nitrite and hydrogen fluoride or fluoroboric acid
-Process for producing fluoroaspartic acid. 3. The manufacturing method according to claim 2, wherein diaminosuccinic acid, sodium nitrite, and hydrogen fluoride are reacted in a pyridine solvent under cooling. 4. The manufacturing method according to claim 2, wherein diaminosuccinic acid, sodium nitrite, and hydrogen fluoride are reacted under cooling. 5. The manufacturing method according to claim 2, wherein diaminosuccinic acid, sodium nitrite, and fluoroboric acid are reacted in an aqueous solution under cooling.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14573476A JPS5944301B2 (en) | 1976-12-03 | 1976-12-03 | β-fluoroaspartic acid and its production method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14573476A JPS5944301B2 (en) | 1976-12-03 | 1976-12-03 | β-fluoroaspartic acid and its production method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5371013A JPS5371013A (en) | 1978-06-24 |
| JPS5944301B2 true JPS5944301B2 (en) | 1984-10-29 |
Family
ID=15391898
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14573476A Expired JPS5944301B2 (en) | 1976-12-03 | 1976-12-03 | β-fluoroaspartic acid and its production method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5944301B2 (en) |
-
1976
- 1976-12-03 JP JP14573476A patent/JPS5944301B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5371013A (en) | 1978-06-24 |
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