JPH04288080A - Production of benzopyrano(2,3-b)pyridine derivative - Google Patents
Production of benzopyrano(2,3-b)pyridine derivativeInfo
- Publication number
- JPH04288080A JPH04288080A JP12695891A JP12695891A JPH04288080A JP H04288080 A JPH04288080 A JP H04288080A JP 12695891 A JP12695891 A JP 12695891A JP 12695891 A JP12695891 A JP 12695891A JP H04288080 A JPH04288080 A JP H04288080A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- benzopyrano
- compound
- aluminum isopropoxide
- solvent
- 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.)
- Pending
Links
- MXIYRNSRKGMBLQ-UHFFFAOYSA-N 5h-chromeno[2,3-b]pyridine Chemical class C1=CC=C2CC3=CC=CC=C3OC2=N1 MXIYRNSRKGMBLQ-UHFFFAOYSA-N 0.000 title abstract description 6
- 238000004519 manufacturing process Methods 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 20
- SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000002904 solvent Substances 0.000 claims abstract description 14
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims abstract description 6
- 238000009835 boiling Methods 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- 150000001491 aromatic compounds Chemical class 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- 150000002430 hydrocarbons Chemical class 0.000 claims 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 abstract description 6
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 abstract description 4
- TVQZAMVBTVNYLA-UHFFFAOYSA-N Pranoprofen Chemical compound C1=CC=C2CC3=CC(C(C(O)=O)C)=CC=C3OC2=N1 TVQZAMVBTVNYLA-UHFFFAOYSA-N 0.000 abstract description 3
- 229960003101 pranoprofen Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 10
- GWHJZXXIDMPWGX-UHFFFAOYSA-N 1,2,4-trimethylbenzene Chemical compound CC1=CC=C(C)C(C)=C1 GWHJZXXIDMPWGX-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-trimethylbenzene Chemical compound CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical group C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 239000012670 alkaline solution Substances 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- KWFWIGXYOMVRSA-UHFFFAOYSA-N chromeno[2,3-b]pyridin-5-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3OC2=N1 KWFWIGXYOMVRSA-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- SQNZJJAZBFDUTD-UHFFFAOYSA-N durene Chemical compound CC1=CC(C)=C(C)C=C1C SQNZJJAZBFDUTD-UHFFFAOYSA-N 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- IBRSSZOHCGUTHI-UHFFFAOYSA-N 2-chloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1Cl IBRSSZOHCGUTHI-UHFFFAOYSA-N 0.000 description 1
- 238000006820 Bouveault-Blanc reduction reaction Methods 0.000 description 1
- 238000006214 Clemmensen reduction reaction Methods 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 238000005644 Wolff-Kishner reduction reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229930007927 cymene Natural products 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- -1 that is Chemical compound 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
【０００１】0001
【技術分野】本発明は、医薬として有用なプラノプロフ
ェンすなわち、α−メチル−５Ｈ−〔１〕ベンゾピラノ
〔２，３−ｂ〕ピリジン−７−イル酢酸の製造用の中間
体である下記式Ｉで表わされる５Ｈ−〔１〕−ベンゾピ
ラノ〔２，３−ｂ〕ピリジン誘導体の製造方法に関する
。[Technical Field] The present invention relates to an intermediate for the production of pranoprofen, that is, α-methyl-5H-[1]benzopyrano[2,3-b]pyridin-7-yl acetic acid, which is useful as a pharmaceutical, and is based on the following formula: The present invention relates to a method for producing a 5H-[1]-benzopyrano[2,3-b]pyridine derivative represented by I.
【０００２】0002
【化３】
（式中、Ｒ１およびＲ２は、それぞれ、同一又は異なっ
て、水素原子又は低級アルキル基を意味する）[Formula 3] (wherein, R1 and R2 are the same or different and each represents a hydrogen atom or a lower alkyl group)
【０００
３】000
3]
【背景技術】式ＩＩ[Background technology] Formula II
【化４】
で表わされる５−オキソ型化合物から式Ｉで表わされる
化合物を製造するために用いられる反応としては、従来
、この種のオキソ型化合物を還元する還元反応として、Conventionally, the reaction used to produce the compound represented by formula I from the 5-oxo type compound represented by the following formula is as follows:
【０００４】（１）Ｂｏｕｖｅａｕｌｔ−Ｂｌａｎｃ還
元
（２）Ｗｏｌｆｆ−Ｋｉｓｈｎｅｒ還元（３）Ｃｌｅｍ
ｍｅｎｓｅｎ還元
（４）接触水素化還元
が考えられ、試みられているが、これらの還元による方
法では、副反応物が生成するために、目的の化合物は極
く微か得られるか、全く得られないかであった（中西美
智夫他、薬学雑誌９６ ９９（１９７６）参照）。(1) Bouveault-Blanc reduction (2) Wolff-Kishner reduction (3) Clem
Mensen Reduction (4) Catalytic hydrogenation reduction has been considered and attempted, but these reduction methods produce only a small amount of the desired compound or cannot be obtained at all due to the formation of side reactants. (Refer to Michio Nakanishi et al., Pharmaceutical Journal 96, 99 (1976)).
【０００５】また、式ＩＩの化合物をアルミニウムイソ
プロポキシドの存在下、イソプロピルアルコールと加熱
するか、又は水素化ホウ素ナトリウムで還元して、式Ｉ
ＩＩで表わされる化合物とし、Compounds of formula II can also be heated with isopropyl alcohol in the presence of aluminum isopropoxide or reduced with sodium borohydride to give formula I
A compound represented by II,
【化５】
（式中Ｒは、水素又はイソプロピル基を示す）次いで式
ＩＩＩの化合物を酸の存在下、イソプロピルアルコール
等と加熱するか、接触水素化還元する方法も知られてい
るが、この方法も２工程を経なければならない方法であ
る（特公昭５７−５８３５３号公報参照）。[Chemical formula 5] (In the formula, R represents hydrogen or an isopropyl group) A method is also known in which the compound of formula III is then heated with isopropyl alcohol or the like in the presence of an acid, or catalytic hydrogenation reduction is carried out. The method also requires two steps (see Japanese Patent Publication No. 57-58353).
【０００６】[0006]
【発明の開示】本発明者らは、先に式ＩＩで表わされる
化合物から、式Ｉで表わされる化合物を無溶媒での反応
によって１工程で効率良く得る方法を見い出したが（特
願平２−２０８０１３号）、この方法は、前記従来の各
方法より優れてはいるものの式ＩＩで表わされる化合物
に対し４倍モル以上のアルミニウムイソプロポキシドを
作用させることが必要であり、かつ収率の点でも、必ず
しも満足し得るものではなかったので、さらに研究を重
ねた結果、当該反応を沸点が１６０℃以上の脂肪族炭化
水素又は芳香族炭化水素を溶媒として用いておこなうこ
とにより、式ＩＩの化合物に対する、アルミニウムイソ
プロポキシドの使用量が減量され、かつ、より高収率で
式Ｉの化合物が得られることを見出した。DISCLOSURE OF THE INVENTION The present inventors have previously discovered a method for efficiently obtaining a compound represented by formula I from a compound represented by formula II in one step by reaction without a solvent. Although this method is superior to the above-mentioned conventional methods, it requires the action of at least 4 times the mole of aluminum isopropoxide on the compound represented by formula II, and the yield is lower. However, as a result of further research, the reaction of formula II was carried out using an aliphatic hydrocarbon or an aromatic hydrocarbon having a boiling point of 160°C or higher as a solvent. It has been found that the amount of aluminum isopropoxide used relative to the compound can be reduced and higher yields of the compound of formula I can be obtained.
【０００７】本発明は、かかる知見に基づいてなされた
ものである。すなわち、本発明は、式ＩＩThe present invention has been made based on this knowledge. That is, the present invention provides formula II
【化６】
（Ｒ１およびＲ２は、それぞれ、同一又は異なって水素
原子又は低級アルキル基を意味する）で表わされる化合
物を沸点が１６０℃以上の脂肪族炭化水素又は芳香族炭
化水素を溶媒として用いてアルミニウムイソプロポキシ
ドと処理することを特徴とする式Ｉ[Chemical formula 6] (R1 and R2 are the same or different and each means a hydrogen atom or a lower alkyl group) using an aliphatic hydrocarbon or aromatic hydrocarbon having a boiling point of 160°C or higher as a solvent. Formula I, characterized in that it is treated with aluminum isopropoxide.
【０００８】[0008]
【化７】
（Ｒ１およびＲ２は、前記の意味を有する）で表わされ
る化合物の製造方法を提供するものである。A method for producing a compound represented by the formula (R1 and R2 have the above-mentioned meanings) is provided.
【０００９】本発明方法は、沸点が１６０℃以上の脂肪
族炭化水素又は芳香族炭化水素を溶媒として用いること
を特徴とするものであり、この特定の溶媒を使用するこ
とにより、無溶媒下で反応を行なう先に提案した方法に
比べて、式ＩＩの化合物に対するアルミニウムイソプロ
ポキシドの使用量が低減され、かつ大幅に収率が向上す
るという格別の効果が奏されるものである。The method of the present invention is characterized by using an aliphatic hydrocarbon or an aromatic hydrocarbon having a boiling point of 160° C. or higher as a solvent. Compared to the previously proposed method of carrying out the reaction, this method has the distinct effect of reducing the amount of aluminum isopropoxide used relative to the compound of formula II and significantly improving the yield.
【００１０】使用される脂肪族炭化水素溶媒としては、
デカンおよびデカリンなどが挙げられ、又芳香族炭化水
素溶媒としては、１，２，４−トリメチルベンゼン、１
，３，５−トリメチルベンゼン、デュレン、シメンおよ
びテトラリンなどが挙げられる。なかでも好ましくは、
１，２，４−トリメチルベンゼンおよび１，３，５−ト
リメチルベンゼンである。[0010] The aliphatic hydrocarbon solvent used is:
Examples of aromatic hydrocarbon solvents include decane and decalin, and examples of aromatic hydrocarbon solvents include 1,2,4-trimethylbenzene, 1
, 3,5-trimethylbenzene, durene, cymene, and tetralin. Among them, preferably
1,2,4-trimethylbenzene and 1,3,5-trimethylbenzene.
【００１１】アルミニウムイソプロポキシドの使用量は
、式ＩＩの化合物に対し、無溶媒下による前述の方法で
は４倍モル以上を必要としたが、本発明方法においては
前記の特定の溶媒を使用することにより、４倍モル以上
を必要とせず、２．４倍モルまで減量しても、目的を達
成することができる。このアルミニウムイソプロポキシ
ドの使用量の低減は、反応後、反応混合物中に混在する
過剰のアルミニウムイソプロポキシドをアルカリ水溶液
で分解するという後処理工程において、アルカリ水溶液
の使用量が少なくなるという利点をももたらすものであ
り、処理操作上の効果のみならず、それにより経済的効
果をももたらすものである。[0011] The amount of aluminum isopropoxide used was 4 times or more in mole relative to the compound of formula II in the above-mentioned method without a solvent, but in the method of the present invention, the above-mentioned specific solvent is used. Therefore, the purpose can be achieved even if the amount is reduced to 2.4 times the mole without requiring more than 4 times the mole. This reduction in the amount of aluminum isopropoxide used has the advantage that after the reaction, the amount of alkaline aqueous solution used is reduced in the post-treatment process in which excess aluminum isopropoxide mixed in the reaction mixture is decomposed with aqueous alkaline solution. This brings about not only effects on processing operations but also economic effects.
【００１２】反応温度は、１４５℃以上使用される溶媒
の沸点までの温度範囲であり、通常は１５０〜１６０℃
で行なわれる。目的化合物の反応混合物からの採取は、
反応液を室温付近まで冷却した後、反応混合物にアルカ
リ水溶液を加えて、反応混合物中に存在する過剰のアル
ミニウムイソプロポキシドを分解させ、この分解により
生成するアルミニウムの無機塩を水層として分離した後
、有機層を水洗し、さらにこの有機層から塩酸水で抽出
し、有機層を分離した後、水層をアルカリ性にして目的
化合物を結晶として析出させ、濾別して得る。得られた
目的化合物は、必要により四塩化炭素等の溶媒で精製さ
れる。[0012] The reaction temperature ranges from 145°C to the boiling point of the solvent used, usually from 150 to 160°C.
It will be held in To collect the target compound from the reaction mixture,
After cooling the reaction solution to around room temperature, an aqueous alkaline solution was added to the reaction mixture to decompose excess aluminum isopropoxide present in the reaction mixture, and the inorganic salt of aluminum produced by this decomposition was separated as an aqueous layer. Thereafter, the organic layer is washed with water, further extracted with aqueous hydrochloric acid, the organic layer is separated, and the aqueous layer is made alkaline to precipitate the target compound as crystals, which are obtained by filtration. The obtained target compound is purified using a solvent such as carbon tetrachloride, if necessary.
【００１３】本発明方法の出発物質である式ＩＩの化合
物は、２−クロロニコチン酸とフェノールとから、Ｊ．
Ｃｈｅｍ．，Ｓｏｃ．，１９５２，２０５７〜２０６２
に記載された方法によって得られる。次に、実施例を掲
げ、本発明を具体的に説明する。The compound of formula II, which is the starting material for the process of the invention, is prepared from 2-chloronicotinic acid and phenol, as described in J.
Chem. , Soc. , 1952, 2057-2062
obtained by the method described in . Next, the present invention will be specifically explained with reference to Examples.
【００１４】[0014]
【実施例】５Ｈ−〔１〕ベンゾピラノ（２，３−ｂ〕ピ
リジンの合成
反応容器に、５−オキソ−５Ｈ−〔１〕ベンゾピラノ〔
２，３−ｂ〕ピリジン３９．４ｇ（０．２００ｍｏｌ）
とアルミニウムイソプロポキシド９６．０ｇ（０．４８
０ｍｏｌ）と１，２，４−トリメチルベンゼンとを入れ
、１５０℃まで昇温させた後、１５０〜１６０℃にて１
０時間反応させる。反応混合物を室温まで冷却した後、
９５％苛性ソーダ２０．２ｇ（０．４８０ｍｏｌ）を水
４００ｍｌに溶かした液の中に、１時間かけて室温にて
滴下し、同温度にて１時間撹拌する。水層を分離後、有
機層を水４００ｍｌで２回洗浄後、１０％塩酸水１４０
ｇにて抽出する。有機層を分離後、水層に２５％安水を
室温にてｐＨ９付近までゆっくりと加える。析出した結
晶を濾過し水１００ｍｌで洗浄後、乾燥し、四塩化炭素
にて精製する。融点８７〜８８℃の５Ｈ−〔１〕ベンゾ
ピラノ〔２，３−ｂ〕ピリジン２６．１ｇ（収率７１．
２％）を得た。[Example] Synthesis of 5H-[1]benzopyrano(2,3-b]pyridine In a reaction vessel, 5-oxo-5H-[1]benzopyrano[
2,3-b]Pyridine 39.4g (0.200mol)
and aluminum isopropoxide 96.0g (0.48
0 mol) and 1,2,4-trimethylbenzene, heated to 150°C, and heated to 150-160°C.
React for 0 hours. After cooling the reaction mixture to room temperature,
The mixture was added dropwise to a solution of 20.2 g (0.480 mol) of 95% caustic soda dissolved in 400 ml of water at room temperature over 1 hour, and stirred at the same temperature for 1 hour. After separating the aqueous layer, the organic layer was washed twice with 400 ml of water, and then washed with 140 ml of 10% hydrochloric acid.
Extract at g. After separating the organic layer, 25% ammonium chloride was slowly added to the aqueous layer at room temperature until the pH reached around 9. The precipitated crystals are filtered, washed with 100 ml of water, dried, and purified with carbon tetrachloride. 26.1 g of 5H-[1]benzopyrano[2,3-b]pyridine with a melting point of 87-88°C (yield 71.
2%).
【００１５】比較例（無溶媒法）
反応容器に、５−オキソ−５Ｈ−〔１〕ベンゾピラノ〔
２，３−ｂ〕ピリジン３９．４ｇ（０．２００ｍｏｌ）
とアルミニウムイソプロポキシド１６３．４ｇ（０．８
００ｍｏｌ）とイソプロピルアルコール１００ｍｌとを
入れ、充分に、混合し、１５０℃まで昇温させた後、１
５０〜１５５℃にて８時間反応させる。反応混合物を９
０℃付近まで冷却した後、トルエン２００ｍｌを用いて
、反応液を希釈する。９５％苛性ソーダ３３．７ｇ（０
．８００ｍｏｌ）を水２００ｍｌに溶かした液の中に、
上記の希釈した反応液を、１時間かけて室温にて滴下し
、１時間、同温度にて撹拌する。次いで、副生したアル
ミニウムの無機塩を濾別し、水層を分離後、トルエン層
を水２００ｍｌで洗浄した後、濃縮し、四塩化炭素にて
精製する。融点８７〜８８℃の５Ｈ−〔１〕ベンゾピラ
ノ〔２，３−ｂ〕ピリジン２１．２ｇ（収率５７．８％
）を得た。Comparative example (solvent-free method) 5-oxo-5H-[1]benzopyrano[
2,3-b]Pyridine 39.4g (0.200mol)
and aluminum isopropoxide 163.4g (0.8
00 mol) and 100 ml of isopropyl alcohol, mix thoroughly, heat up to 150°C, and then add 100 ml of isopropyl alcohol.
React at 50-155°C for 8 hours. 9 of the reaction mixture
After cooling to around 0°C, the reaction solution is diluted with 200 ml of toluene. 95% caustic soda 33.7g (0
．． 800 mol) dissolved in 200 ml of water,
The above diluted reaction solution was added dropwise at room temperature over 1 hour, and stirred at the same temperature for 1 hour. Next, the by-produced inorganic salt of aluminum is filtered off, the aqueous layer is separated, and the toluene layer is washed with 200 ml of water, concentrated, and purified with carbon tetrachloride. 21.2 g of 5H-[1]benzopyrano[2,3-b]pyridine with a melting point of 87-88°C (yield 57.8%)
) was obtained.
Claims (1)
原子又は低級アルキル基を意味する）で表わされる化合
物を沸点が１６０℃以上の脂肪族炭化水素又は芳香族炭
化水素を溶媒として用いて、アルミニウムイソプロポキ
シドと処理することを特徴とする式Ｉ 【化２】 （Ｒ１およびＲ２は、前記の意味を有する）で表わされ
る化合物の製造方法。Claim 1: A compound represented by formula II [Formula 1] (R1 and R2 are the same or different and each represents a hydrogen atom or a lower alkyl group) is an aliphatic hydrocarbon or an aromatic compound having a boiling point of 160°C or higher. A process for producing a compound of the formula I embedded image (R1 and R2 have the meanings given above), which comprises treating with aluminum isopropoxide using a group hydrocarbon as a solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12695891A JPH04288080A (en) | 1991-03-13 | 1991-03-13 | Production of benzopyrano(2,3-b)pyridine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12695891A JPH04288080A (en) | 1991-03-13 | 1991-03-13 | Production of benzopyrano(2,3-b)pyridine derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04288080A true JPH04288080A (en) | 1992-10-13 |
Family
ID=14948110
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP12695891A Pending JPH04288080A (en) | 1991-03-13 | 1991-03-13 | Production of benzopyrano(2,3-b)pyridine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04288080A (en) |
-
1991
- 1991-03-13 JP JP12695891A patent/JPH04288080A/en active Pending
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