Method of obtaining 5-substituted 1,2-dihydro-3h-pyrrolo-(1,2-a)-pyrrol-1-carbonic acids

专利摘要:
METHOD OF OBTAINING 5-SUBSTITUTED 1,2-DIHYDRO-ZN-PIRROLO-
公开号:SU1138029A3
申请号:SU782641055
申请日:1978-07-24
公开日:1985-01-30
发明作者:Р.Ван Хорн Альберт；Г.Галлегра Паскуале
申请人:Синтекс (Ю.С.А.) Инк.(Фирма)；
IPC主号:

专利说明:

for 7 minutes, keeping it under nitrogen, cooled to room temperature and 10 ml of cold water (at 4 ° C) is added to it. The reaction mixture is then extracted twice with 5 ml portions of ethyl acetate. The ethyl acetate extracts were dried over anhydrous sodium sulfate, then the solvent was completely evaporated to give 0.32 g (102%) of crude product (93% purity, as measured by high pressure liquid chromatography) containing 5- (2-tenosh1) -1,2-dihydro-ZN-pyrrolo (1,2) -pyrrole-1-carboxylic acid.
0.2 g of the resulting 5- (2-toenoip) 1, 2-dihydro-3H-pyrrolo (1,2-a) pyrrole-1-carboxylic acid is dissolved in 3 ml of ethyl acetate and 1 ml of methanol and 0.2 g bleaching charcoal. The mixture is heated to 50 ° C, then the charcoal is separated by filtration, and the methanol is distilled off. The remaining solution is brought to approximately 2 ml by adding ethyl acetate, then it is cooled to and separated by filtration 0.17 g (85%), 95% pure (by liquid chromatography at high pressure) 5- (2-thenoyl) 1 , 2-dihydroZN-pyrrolo (1,2-a) -pyrrole-1-carboxylic acid, which has so pl. 154-155 ° C. Additional quantities of the product can be obtained from the mother liquor according to the developed crystallization methods.
Similarly, replacing concentrated hydrochloric acid (37% aqueous solution) with a stoichiometric equivalent of sulfuric acid (40% aqueous), 5- (2-tenosh) 1, 2-dihydro-3H-pyrrolo (1,2 -a) -pyrrole- 1-carboxylic acid.
Pf and meper 2; To 3.5 g of 60% aqueous sulfuric acid, 0.5 g of 5- (2-thooyl) -1,2-dihydro 3 H-pyrrolo (1,2-a) pyrrole-1 is added. nitrile. The reaction mixture is purged with nitrogen and heated to. The reaction mixture is stirred for 12 minutes, held in a nitrogen atmosphere and 10 ml of cold water (at 4 ° C) is added to it. The reaction mixture is then extracted with two 5 ml portions of ethyladetate. Ethyl acetate
the extracts are combined, dried over anhydrous sodium sulfate, and concentrated to dryness to obtain 0.5 g (92.7%) of crude product (56% purity, as shown by liquid chromatography under pressure) containing 5- (2-thenoyl ) 1,2-dihydro-3H-pyrrolo (1,2-a) pyrrol-1-carboxylic acid.
0.4 g of the crude product thus obtained is dissolved in 4 ml of methanol and 4 ml of water are added thereto. The mixture is stirred and then filtered. So implemented
the solid residue is dissolved in 5 ml of ethyl acetate and 1 ml of methanol, and 0.5 g of bleaching charcoal is added to the solution. The mixture is heated to 50c, the charcoal is filtered off and the methanol is removed. Then the volume of the solution is made up to 2 ml by adding ethyl acetate, and 0.2 g (50%) is obtained by subsequent cooling to and filtering.
5- (2-thenoyl) -1,2-dihydro-3H-pyrrolo (1,2-a) -pyrrole-1-carboxylic acid, which has so pl. 147-148 ° C. The melting point remained the same after the second recrystallization from ethyl acetate, and high pressure liquid chromatography showed that the purity of the product was
7Q W / O, OA.
Example Z.K a mixture of 8 ml of ice
acetic acid and 8 MP 85%
phosphoric acid, 1.6 g of 5- (2-thenoyl) -1,2-dihydro-3H-pyrrolo (1,2-a) -pyrrol-1-nitrile are added. The reaction mixture is purged with nitrogen and held in a nitrogen atmosphere at 110115 ° C for 2. h and 20 min. The reaction mixture is cooled and added to 50 ml of a mixture of 70% aqueous saturated sodium chloride solution and 30% water. The precipitated substance is ext. 1 was discarded with 10 ml of ethyl acetate, and the extract was dried over anhydrous sodium sulfate and concentrated, removing almost all of the solvent. Then add 20 ml of hekoane, filter, dry under vacuum at 45 s to obtain 1.66 g (96.3%) of crude product (purity 79% as shown by
high pressure liquid chromatography) containing 5- (2-thenoyl) 1, 2-dihydro-3H-pyrrolo- (1,2-a) -pyrrole-1-carboxylic acid. 1.4 g of the product thus obtained is dissolved in 15 ml. methanol and 0.5 decolorizing charcoal is added to the solution. The mixture is stirred for 15 minutes. Charcoal is filtered off, the solution is concentrated to a volume of 5 ml, and 5 ml of water is added to it. The aqueous mixture was stirred for 10 minutes and then filbTpiTOT to obtain 1.1 g (78.6%) of product containing 5- (2-thenoyl) -1,2-dihydro-3H-pyrrol-1-carboxylic acid. 1.0 g of this product is dissolved in 6 MP of hot ethyl acetate and the mixture is cooled to, stirred for 15 minutes, then filtered and washed with 2 ml of cold () ethyl acetate, to obtain 0.6 g (60%) of 5- (2-coyl ) -1,2-dihydro-ZN-pyrrolo (1,2-a pyrrole-1-carboxylic acid, which has a melting point of 158-159 C. Additional product quantities can be obtained from this ethyl acetate solution using standard crystallization techniques. Example 4. 2-methoxyethanol is added 0.8 g of 5- (2-thenoyl) -1,2-dihydro-3H-pyrrolo (1,2-a) pyrrol-1-nitrile. After purging the reaction mixture with nitrogen 1.6 ml of a 20% aqueous solution of potassium hydroxide are added, and the reaction mixture is boiled under nitrogen atmosphere for 48 minutes. The reaction mixture is cooled to 20 ° C and 10 MP of water are added to it, then washed 20 mp methylene chloride. To the aqueous portion, after extraction, concentrated hydrochloric acid is added to maintain a pH of about 3 and the precipitated substance is extracted with 20 MP of ethyl acetate, dried over anhydrous sodium sulfate and concentrated to a dry state. 0.776 g (90%) is obtained. the crude product containing 5- (2-thenoyl) -1,2-dihydro-3H-pyrrolo- (1 ,, 2-a) -pyrrole o-1 -carboxylic acid. 0.45 g of the crude product is dissolved in 5 MP of hot ethyl acetate, the solution is cooled to, stirred for 5 minutes, then filtered, washed with 2 ml of a mixture of ethyl acetate and hexane 2: 1, and dried under vacuum at 45 ° C. Obtain g (71 wt.%) 5- (2-tenoyl) -1,2-dihydroZN-pyrrolo-. (1,2-a) -pyrrol-1-carboic acid, which has so pl. . Additional amounts of the product can be obtained by using a standard developed crystallization unit. Similarly, by replacing the hydroxide with a stoichiometric equivalent of sodium hydroxide or lithium oxide, 5- (2-bodies) -1,2-dihydro-3H-pyrrole- (1,2-a) rol-1-carboxylic acid are obtained. Example 5. Following the procedures given in examples 1-4, and replacing 5- (2-thenoyl) -1,2-digilro-3H-pyro- (1,2-a) -pyrrole-1-nitrile for stoichi tric-equivalent amounts Ingredients: 5-benzoyl-1,2-dihydro-ZN-pyrrolo- (1,2-a) -pyrrol-1-nitrile 5-0-Toluoyl-1,2-dihydro-ZNpyrrolo- (1,2-a) -pyrrol-1-nitrile 5-M-Toluyol-1,2-dihydro-Znpyrrolo- (1,2-a) -pyrrol-1 -latryl 5-P-Toluoyl-1,2-dihydro-Znpyrrole- (1, 2-a) -pyrrol-1-niterkl 5-p-methoxybenzoyl-1,2-dihydro-3H-pyrrolo- (1,2-a) pyrrol-1-nitrile. 5-p-ethoxybenzoyl-1,2-dihydro-ZN-pyrrolo- (1,2-a) -pyrrol1-nitrile 5-0-chlorobenzoyl-1,2-dihydroZN-pyrrolo- (1,2-a) -pyrrol1 -nitrile 5-m-chlorobenzoyl-1,2-dihydroZN-pyrrolo- (1,2-a) -pyrrol1-nitrile 5-P-chlorobenzoyl-1,2-5HydroZN-pyrrolo- (1,2-a) -lyrrole -nitrile 5-0-fluorobenzoyl-1,2-dihydro ZN-pyrrolo- (1,2-a) -pyrrol1-nitrile 5- (1-fluorobenzoyl-1,2-dihydroZN-pyrrolo- (1,2-a) -pyrrol1-nitrile 5-p-fluorobenzoyl-1,2-dihydroZN-pyrrolo- (1,2-a) -pyrrol1-nitrile 5- (3-chloro-2-te.noyl) -1,2-dihydro-3N -pyrrolo (1,2-a) pyroprol-1-nitropyl 5- (4-chloro-2-tenoyl) -1,2-dihydro-3H-pyrrolol- (1, 2-a) pyrrole-1-nitrile 5- ( 5-chloro-2-thenoyl) -1,2-dihydro-3H-pyropolo- (1, 2-a) pyrrole-1-nitrile

权利要求:
Claims (1)
[1]
METHOD FOR PRODUCING 5-SUBSTITUTED 1,2-DIHYDRO-ZN-PYRROLO- (1,2-a) PYRROL-1-CARBONIC ACIDS of the general formula -
0.
- -.-- v- where V - is by hydrolysis of the corresponding carboxylic acid derivative, characterized in that, in order to simplify the process, increase the yield and expand the assortment of the target products, the nitrile carboxylic acid is subjected to hydrolysis of the general formula where _} R, R] and Rg have the indicated meanings.
SU, _m 1138029 ί

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法律状态:

优先权:

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申请号 | 申请日 | 专利标题

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US81837777A| true| 1977-07-25|1977-07-25|

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