Category: 3891-07-4

3891-07-4, name is 2-(2-Hydroxyethyl)isoindoline-1,3-dione, belongs to indolines-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Recommanded Product: 2-(2-Hydroxyethyl)isoindoline-1,3-dione

a synthetic process of amlodipine besylate,The difference from Embodiment 1 is thatStep 2 specifically includes:In the reaction tank,Put 350kg of toluene,Stirring,Distilling toluene,After the liquid in the water separator is full,Keep the reflux water for 60 minutes,Sampling to determine water separation,When the water content of the reflux liquid is ?0.2%,Change the reflux to distillation,Distilling off toluene,Stir and cool down,When the temperature inside the tank drops to 45 C,Filling the reaction tank with nitrogen,Continue to cool down to 5 C,40 kg of N-(2-hydroxyethyl)-phthalimide was added with stirring.Then add 20kg of sodium hydride,Plus,Close the lid,Stir at 5 C,38.4 kg of ethyl 4-chloroacetoacetate was taken in the measuring tank.45kg of toluene and mix well,Drop into the reaction tank at 5 CAdd a solution of ethyl 4-chloroacetoacetate in toluene,The dripping time is controlled at 4 hours.Plus,Continue to stir the reaction for 2 hours.Slowly warming up,The temperature of the reaction solution was slowly raised to 38 C within 5 hours.The reaction time is more than 12 hours.Warm up to 51 C and keep warm for 1 hour.Until the reaction is complete,Cooling down,Control the internal temperature of 35 C,Add 61kg glacial acetic acid,Plus,Stirring was continued for 60 minutes to stir the material in the reaction solution evenly.The internal temperature is controlled at 35 C.Add 180kg of water,Plus,Continue to stir for 30 minutes.Stop filling with nitrogen,Stop stirring,Stand still and separate the water layer into the bucket.Transfer the toluene layer to the washing tank,Transfer the water layer to the reaction tank,Add 75 kg of toluene to the reaction tank.Stir,Stand still and separate the water layer into the bucket.Then transfer the toluene layer to the washing tank.Transfer the water layer to the reaction tank,Add 75 kg of toluene to the reaction tank.Stir,Rest,Separate the water layer,Combine the toluene layer into a water wash tank,Add 100kg of 25% salt water to the washing tank.Stir for 15 minutes,Let stand for 30 minutes,Divided into the water layer,Toluene solution of 4-[(2-phthalimido)ethoxy]acetic acid ethyl acetate;The yield of amlodipine besylate was 91.1%, and the purity was 99.3%.

The synthetic route of 3891-07-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shanghai Fenglin Biological Technology Co., Ltd.; Zheng Yulin; Chen Yushuang; Liu Lijuan; Gao Huanhuan; Yu Yaoying; (13 pag.)CN108456160; (2018); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 3891-07-4,Some common heterocyclic compound, 3891-07-4, name is 2-(2-Hydroxyethyl)isoindoline-1,3-dione, molecular formula is C10H9NO3, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Activation of 2-(2-hydroxyethyl)isoindoline-1,3-dione to Form VA To the mixture of commercially available 2-(2-hydroxyethyl) isoindoline-1,3-dione (8.8 g. 1.00 equiv) and triethylamine (5.8 g, 1.25 equiv) in methylene chloride (69 mL) is added benzenesulfonyl chloride (9.3 g, 1.05 equiv) dropwise at under about 25 C. The mixture is stirred at room temperature until the reaction is complete as determined by HPLC. The reaction mixture is washed with an aqueous solution of sodium bicarbonate. The organic solution is concentrated under reduced pressure and the product is precipitated by adding hexanes (83 mL) to the residue. VA is isolated by filtration (15.1 g, 99% yield). 1H NMR (400 MHz, DMSO-d6): delta 7.77-7.82 (m, 4H), 7.71 (d, J=8.0, 2H), 7.52 (t, J=8.0, 1H), 7.41 (t, J=8.0, 2H), 4.29 (t, J=4.0, 2H), 3.81 (t, J=4.0, 2H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-(2-Hydroxyethyl)isoindoline-1,3-dione, its application will become more common.

Reference:
Patent; Gilead Sciences, Inc.; Chiu, Anna; Feng, Yanshu; Gao, Hanrong; Kerschen, James A.; Reichwein, John; Sarma, Keshab; Thompson, Andrew S.; Zhao, Xinjun; US2015/225384; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 3891-07-4,Some common heterocyclic compound, 3891-07-4, name is 2-(2-Hydroxyethyl)isoindoline-1,3-dione, molecular formula is C10H9NO3, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

This compound was obtained by mixing fuming nitric acid (1.0 mmol) and the precursor compound (0.10 mmol) at – 5 C and stirring for 2 h (Scheme 1). The reaction mixture was poured into a mixture of water and ice. The pH was adjusted to 6 by adding CaCO3. The obtained white solid was vacuum filtered, with yield 93%; Mp 87.1-89.5 C. IR (ATR): 3062, 3030, 2978, 2886, 1774, 1716, 1608, 1422, 1402, 1288, 982, 870, 722, 530. 1H NMR (200 MHz, DMSO-d6): 3.95 (t, 2H), 4.71 (t, 2H), 7.86 (br s,4H). 13C NMR (50 MHz, DMSO-d6): 34.8, 70.8, 123.1, 131.4, 134.4, 167.5. Anal. Calcd. for C10H8N2O5. Calcd. (%): C, 50.85; H, 3.41; N, 11.86. Found (%): C, 51.09; H, 3.32; N, 11.77.

The synthetic route of 3891-07-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Godin, Adriana M.; Araujo, Debora P.; Menezes, Raquel R.; Brito, Ana Mercy S.; Melo, Ivo S.F.; Coura, Giovanna M.E.; Soares, Darly G.; Bastos, Leandro F.S.; Amaral, Flavio A.; Ribeiro, Lucas S.; Boff, Daiane; Santos, Julliana R.A.; Santos, Daniel A.; Teixeira, Mauro M.; De Fatima, Angelo; Machado, Renes R.; Coelho, Marcio M.; Pharmacology, Biochemistry and Behavior; vol. 122; (2014); p. 291 – 298;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 3891-07-4, name is 2-(2-Hydroxyethyl)isoindoline-1,3-dione, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. category: indolines-derivatives

To a mechanically stirred suspension of NaH (15g, 0. 375 mol, 60% dispersion in mineral oil) in THF (250 mL) and DMF (25 mL) was added N- (2-hydroxyethyl)-phtalimide (43g, 0. 225 mol). The mixture was stirred at room temperature for about 4 h and then cooled to about 0C in an ice bath. Ethyl-4- chloroacetate (21. 4 mL, 0. 15 mol) in THF (4 mL) was then added via an addition funnel over a period of about 0. 5 h and the resulting mixture allowed to stir overnight. The mixture was then poured into a 2 L sepratory funnel containing 500 mL ice water and 700 mL EtOAc and separated. The organic layer was washed 2x with 500 mL of water and dried over MGS04. The solution was then filtered through a 4-inch plug of silica and then CONCENTRATED IN VACUO. The resulting yellow oil was then dissolved in 250 mL CH3CN and washed 2x with 30 mL hexane. The CH3CN layer was the concentrated in vacuo to yield 19. 4g (40. 5%) OF 4- [2- (1, 3-DIOXO-1, 3-DIHYDRO-ISOINDOL-2-YL)-ETHOXY]-3-OXO-BUTYRIC acid ethyl ester as a yellow oil. This crude compound was used for the next step

The synthetic route of 2-(2-Hydroxyethyl)isoindoline-1,3-dione has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SYNTA PHAMACEUTICALS CORP.; WO2005/25507; (2005); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 3891-07-4, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 3891-07-4 as follows.

To a mechanically stirred suspension of NaH (15g, 0. 375 mol, 60% dispersion in mineral oil) in THF (250 mL) and DMF (25 mL) was added N- (2-hydroxyethyl)-phtalimide (43g, 0. 225 mol). The mixture was stirred at room temperature for about 4 h and then cooled to about 0C in an ice bath. Ethyl-4- chloroacetate (21. 4 mL, 0. 15 mol) in THF (4 mL) was then added via an addition funnel over a period of about 0. 5 h and the resulting mixture allowed to stir overnight. The mixture was then poured into a 2 L sepratory funnel containing 500 mL ice water and 700 mL EtOAc and separated. The organic layer was washed 2x with 500 mL of water and dried over MGS04. The solution was then filtered through a 4-inch plug of silica and then CONCENTRATED IN VACUO. The resulting yellow oil was then dissolved in 250 mL CH3CN and washed 2x with 30 mL hexane. The CH3CN layer was the concentrated in vacuo to yield 19. 4g (40. 5%) OF 4- [2- (1, 3-DIOXO-1, 3-DIHYDRO-ISOINDOL-2-YL)-ETHOXY]-3-OXO-BUTYRIC acid ethyl ester as a yellow oil. This crude compound was used for the next step

According to the analysis of related databases, 3891-07-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SYNTA PHAMACEUTICALS CORP.; WO2005/25507; (2005); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem