Author: Jessica.F

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 774-47-0, name is 5,6-Difluoroindoline-2,3-dione, A new synthetic method of this compound is introduced below., Application In Synthesis of 5,6-Difluoroindoline-2,3-dione

The 5,6-difluoro isatin(1.83g, 10mmol)Add 10 mL of acetonitrile to a 100 mL round bottom flask.N-methylpiperazine (1.10 g, 11 mmol) was added dropwise, followed by stirring at room temperature for 4 h. After the reaction was monitored by TLC, purification by column chromatography gave a red solid with a yield of 48%.

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; Sun Yat-sen University; Huang Zhishu; Tan Jiaheng; Che Tong; (27 pag.)CN107540662; (2018); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Electric Literature of 4702-13-0,Some common heterocyclic compound, 4702-13-0, name is N-Phthaloylglycine, molecular formula is C10H7NO4, 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.

In the (G2a) step, 2 mol of thionylchloride (SOCl2) was added to the compound 1a to produce 2-(1,3-dioxoisoindolin-2-yl)acetic chloride (compound 2a) and the unreacted thionylchloride (SOCl2) was recovered by using an aspirator.

The synthetic route of 4702-13-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; THERMOLON KOREA CO.,LTD.; WO2009/131324; (2009); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 7699-18-5,Some common heterocyclic compound, 7699-18-5, name is 5-Methoxyindolin-2-one, molecular formula is C9H9NO2, 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.

General procedure: To a Schlenk tube were added oxindole 1 (0.3 mmol), t-BuONO (0.6 mmol), andTHF (2 mL). Then the tube was stirred at 50 C under 1 atm of O2 for the indicatedtime until complete consumption of starting material monitored by TLC analysis.After the reaction was finished, the reaction mixture was washed with brine. The aqueous phase was re-extracted with ethyl acetate. The combined organic extractswere dried over Na2SO4, removal of the solvent under vacuum afforded the crudeproduct, which was purified further by column chromatography using hexane-ethylacetate.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Methoxyindolin-2-one, its application will become more common.

Reference:
Article; Wei, Wen-Ting; Ying, Wei-Wei; Zhu, Wen-Ming; Wu, Yi; Huang, Yi-Ling; Cao, Yi-Qi; Wang, Yi-Ning; Liang, Hongze; Synlett; vol. 28; 17; (2017); p. 2307 – 2310;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

496-12-8, name is Isoindoline, 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. SDS of cas: 496-12-8

To a suspension of 2-[4-(2-bromoethoxy)-3,5-dimethylphenyl]-5,7-dimethoxy-3H-quinazolin-4-one (0.50 g, 1.15 mmol) in anhydrous DMF (9 mL) was added isoindoline (0.41 mL, 3.46 mmol) and the reaction mixture was stirred at room temperature for 16 hours under nitrogen. The solvent was removed under reduced pressure and the residue was triturated with water (50 mL). The separated solid was filtered, washed with water and ether, and dried under vacuum to give the title compound as a white solid. Yield: 0.45 g (83%). MP 202-202.5 C. 1H NMR (400 MHz, CDCl3): delta 10.09 (br s, 1H), 7.77 (s, 2H), 7.22 (br s, 4H), 6.83 (d, J=2.4 Hz, 1H), 6.46 (d, J=2.4 Hz, 1H), 4.11 (s, 4H), 4.03 (t, J=6.0 Hz, 2H), 3.96 (s, 3H), 3.93 (s, 3H), 3.22 (t, J=6.0 Hz, 2H), 2.42 (s, 6H)

The synthetic route of 496-12-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; RVX Therapeutics Inc.; McLure, Kevin G.; Young, Peter R.; US2013/281399; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 356068-93-4, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 356068-93-4 name is (Z)-5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

To a stirred solution of compound 1 (0.5 g, 1.67 mmol) in DMF (35 rnL) at room temperature was added etaOBt (1.02 g, 7.52 mmol), triethylamine (2.12 mL, 15.03 mmol), ECDIetaC1 (1.44 g, 1.52 mmol) and methyl 6-aminohexanate hydrochloride(0.91 g, 5.0 mmol) successively. The mixture was stirred for 24 h at room temperature and then was diluted with water (20 mL), brine (20 mL) and saturated bicarbonate solution (20 mL) and the peta of solution was adjusted to 11-12 with 10 M NaOH. The mixture was filtrated and the resulting solid was washed with water and dried to obtain crude yellow solid product 110-4 (0.47 g, 65.8%). LCMS: m/z 428(M+1), 1H NMR(DMSO-J6) deltal.33 (m, 2eta), 1.54 (m, 4H), 2.32 (t, 2H), 2.42(s, 3H), 2.50(s, 3H), 3.20( t, 2H), 3.59 (s, 3H), 6.85 (m, 2H), 7.60 (t, IH), 7.69 (s, IH), 7.71 (m, IH), 10.88 (s, IH), 13.67 (s, IH).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, (Z)-5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; CURIS, INC.; WO2008/33747; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 88150-75-8, name is Ethyl 4-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)-3-oxobutanoate belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. Safety of Ethyl 4-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)-3-oxobutanoate

Preparation of ETHYL 2-(2-CHLOROBENZYLIDINE)-4-[2-(PHTHALIMIDE) ETHOXY] ACETOACETATE (XV : A 250 mL two-necked flask, equipped with a magnetic stirring bar and thermometer was charged with 10 g of ethyl 4- [2- (phthalimido) ethoxy] acetoacetate and 3.96 g 2- chlorobenzaldehyde and 100 mL isopropanol under nitrogen atmosphere. To the resulting mixture was added 0.188 ML of acetic acid and 0.223 ML pyrolidine. The reaction mixture was heated to 37 C and stirred at this temperature for 5 hours. The solvent was removed in vacuo and the residue was dissolved in 100 ML of methylene chloride. The resulting solution was washed with 100 mL of sat. NAHCO3 and 100 mL of water, dried over 5 G OF MGS04. MGS04 was filtered off, the filtrate was concentrated in vacuo. The residue was purified by flash chromatography using ethyl acetate/hexane (20/80) as an eluent to give 7.72 g of ethyl 2- (2-CHLOROBENZYLIDINE)-4- [2- (PHTHALIMIDE) ethoxy] acetoacetate as an light brown oil (yield 56%, rel. compound purity > 98%). 1H-NMR (CDCL3) No. 7.89 (s, 1H), 7.78 (dd, 2H), 7.69 (dd, 2H), 7.35 (M, 1H), 7.28 (M, 2H), 7.17 (M, 1H), 4.44 (s, 2H), 4.05 (Q, 2H), 3.76 (T, 2H), 3.64 (t, 2H), 1.20 (t, 3H). 13C-NMR (CDCI3) 6 203. 2,168. 4,164. 0,140. 0,134. 0,133. 9,132. 3,131. 5, 130.4, 129.8, 127.3, 126.8, 123.4, 77.7, 68.5, 62.0, 37.4, 14.3.

The synthetic route of 88150-75-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; EOS ECZACIBASI OZGUN KIMYASAL URUNLER SANAYI VE TICARET A.S.; WO2004/58711; (2004); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 5181-35-1, name is 2-(2-Bromoethoxy)isoindoline-1,3-dione, molecular formula is C10H8BrNO3, 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. Product Details of 5181-35-1

To a solution of 2-(2- bromoethoxy)isoindoline- l,3-dione (5 g, 1.85 mmol, product from step 1 of preparation 10) and lH-tetrazole (1.3 g, 1.85 mmol) in dimethylformamide (25 ml) was added cesium carbonate (6.0 g, 1.85 mmol) in a lot wise under stirring at room temperature. The progress of reaction was monitored by performing thin layer chromatography using mixture of acetone and hexane (3.5:6.5) as solvent. After 16 hours the completion of the reaction was confirmed by thin layer chromatography. The reaction mixture was slowly poured into chilled water (200 ml) under stirring. After stirring for 30 minutes, the precipitates formed were filtered and washed with water (50 ml). The solid compound was dried at 40 C for 2 hours under high vacuum to provide 3.2 g of a mixture of 2-[2-(lH-tetrazol- l-yl)ethoxy]- lH-isoindole- l,3(2H)-dione and 2-[2-(2H-tetrazol-2- yl)ethoxy]- lH-isoindole- l,3(2H)-dione in 66% yield. Analysis: Mass: 260 (M+l) for Molecular weight: 259 and for Molecular formula: C11H9N5O3; To a flask containing mixture of 2-[2-(lH-tetrazol- l-yl)ethoxy]- lH-isoindole- l,3(2H)- dione and 2-[2-(2H-tetrazol-2-yl)ethoxy]- lH-isoindole- l,3(2H)-dione (3.0 g, 1.15 mmol, product from step 1) in dichloromethane (30 ml) was added hydrazine hydrate (0.870 ml, 1.73 mmol) at 25-30 C under stirring and continued stirring for 2 hours. The progress of reaction was monitored by thin layer chromatography. After complete conversion, the unwanted solid was filtered out and washed with dichloromethane (12 ml). The filtrate was concentrated at 40 C under high vacuum to obtain 1.5 g of crude mixture of l-[2-(aminooxy)ethyl]- lH-tetrazole and 2-[2-(aminooxy)ethyl]- 2H-tetrazole (about 100 % yield) and used without further purification in the next step.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5181-35-1, its application will become more common.

Reference:
Patent; WOCKHARDT LIMITED; TADIPARTHI, Ravikumar; PATIL, Vijaykumar Jagdishwar; DEKHANE, Deepak; SHAIKH, Mohammad Usman; BIRAJDAR, Satish; DOND, Bharat; PATEL, Mahesh Vithalbhai; (100 pag.)WO2017/81615; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 675109-26-9, name is 6-Bromoisoindolin-1-one, belongs to indolines-derivatives compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 675109-26-9, Quality Control of 6-Bromoisoindolin-1-one

A mixture of 6-bromoisoindolin-i-one (5 g, 23.6 mmol), sodium azide (3.07 g, 47.2 mmol), sodium ascorbate (234 mg, 1.18 mmol), Cul (450 mg, 2.36 mmol) and trans-N,N-dimethyl- 1 ,2-diaminocyclohexane (504 mg, 3.54 mmol) in ethanol (35 mE) and water (15 mE) was stirred at reflux for 5.5 h under nitrogen. The reaction mixture was allowed to cool to room temperature and extracted with EtOAc (100 mEx3). The combined organic fractions were washed with brine and dried with anhydrous sodium sulfate.The solvent was evaporated under reduced pressure and the residue was purified by chromatography on silica gel (10- 50% EtOAc in pet. ether) to give iSA (1.2 g, 29% yield) as an off-white solid. ESI mlz 175.0 [M+i].

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Bromoisoindolin-1-one, and friends who are interested can also refer to it.

Reference:
Patent; Seal Rock Therapeutics, Inc.; BROWN, Samuel David; US2018/291002; (2018); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

These common heterocyclic compound, 550-44-7, name is 2-Methylisoindoline-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. Application In Synthesis of 2-Methylisoindoline-1,3-dione

Add a nitrating agent to N-methylphthalimide at -5 C, and react at 40 C for 4h, then extract with an extraction solvent dry,N-methyl-4-nitrophthalimide is formed.The extraction solvent is ethyl acetate and dichloromethane, and the weight ratio is 1: 0.6. The weight ratio of the extraction solvent and N-methylphthalimide is 1: 1.

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

Reference:
Patent; Shandong Juancheng Fangyuan Bearing Chemical Co., Ltd.; Li Zhi; Zhang Hongyuan; Zhang Heji; (13 pag.)CN110437131; (2019); A;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 17564-64-6, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 17564-64-6, name is 2-(Chloromethyl)isoindoline-1,3-dione, This compound has unique chemical properties. The synthetic route is as follows.

A mixture of phthalimide (41.14 g, 0.30 mol) and distilled water (100 mL) was stirred for 10 min at room temperature. After addition of formaldehyde solution (40%, 27 mL, 0.36 mol), the resulting solution was refluxed for 1.5 h. After cooling to 0-5 C, the resulting precipitate was collected by filtration, washed with cold water (0-5 C, 200 mL) and dried in air to give the corresponding N-hydroxymethylphthalimide (51.01 g, 96% yield).(0010)A solution of thionyl chloride (23.0 mL, 37.7 g, 0.32 mol) in dichloromethane (50 mL) was slowly added to a mixture of the resulting N-hydroxymethylphthalimide and dichloromethane (550 mL) and N,N-dimethylformamide (350 mL) during 30 min at room temperature with stirring. The resulting mixture was further stirred for 2 h at room temperature. After cooling to 0 C, water (200 mL) was added slowly. And the solution was neutralized to pH 6.7-7.0 by using saturated aqueous NaHCO3 solution. The organic layer was separated and then was dried over anhydrous magnesium sulfate. After evaporation of the solvent under the reduced pressure, the residue was washed with n-hexane (100 mL) to give N-chloromethylphthalimide (51.4 g, 93% yield).(0011) N-Chloromethylphthalimide (51.0 g, 0.26 mol) was dissolved in acetone (500 mL) and potassium O-ethyl xanthate (43.9 g, 274 mmol) was added portionwise in an ice water bath under stirring. The resulting solution was further stirred for 10 h at room temperature. After removal of the solvent, the residue was dissolved in dichloromethane. The resulting solution was washed with water and dried over sodium sulfate. After removal of the solvent under the reduced pressure, pale yellow solid was obtained and recrystallized from ethyl acetate to afford the xanthate 1 as colorless crystals 67.2 g, 92% yield, mp: 99-100 C. Lit.20 mp: 94-95 C. 1H NMR (CDCl3, 400 MHz) (delta, ppm) 1.47 (t, J=7.1 Hz, 3H, CH3), 4.68 (q, J=7.1 Hz, 2H, CH2), 5.34 (s, 2H, CH2), 7.75 (dd, J=5.5, 3.1 Hz, 2H, ArH), 7.88 (dd, J=5.5, 3.1 Hz, 2H, ArH). 13C NMR (CDCl3, 100 MHz) (delta, ppm) 13.7, 41.2, 70.5, 123.6, 131.8, 134.4, 166.6, 210.2.

The chemical industry reduces the impact on the environment during synthesis 2-(Chloromethyl)isoindoline-1,3-dione. I believe this compound will play a more active role in future production and life.

Reference:
Article; Huang, Zhongyan; Xu, Jiaxi; Tetrahedron; vol. 69; 3; (2013); p. 1050 – 1056;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem