Category: 201940-08-1

Application of 201940-08-1,Some common heterocyclic compound, 201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, molecular formula is C13H16BrNO2, 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.

Under nitrogen protection,A solution of 5-bromo-2- (tert-butoxycarbonyl) isoindoline (1.2 g, 4 mmol)And boronic acid pinacol ester (2 g, 8 mmol)Was dissolved in dimethylsulfoxide (20 mL)To this was added potassium acetate (1.6 g, 16 mmol) andPd (dppf) Cl2CH2Cl2 (327 mg, 0.4 mmol).The reaction solution was heated and stirred at 90 C for 12 hours,Cool to room temperature and pour into acetic acidEthyl acetate / water (300 mL / 100 mL), the separated organic phase was washed with brine (100 mL), dried over anhydrous sodium sulfate,Filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 20/1)The title compound was obtained as a yellow oil (1 g, 73%).

The synthetic route of 201940-08-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Jiatuo Sciences Corporation; Xi Ning; Wang Ruyong; Wang Liang; (112 pag.)CN104016979; (2017); B;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 201940-08-1,Some common heterocyclic compound, 201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, molecular formula is C13H16BrNO2, 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.

To a suspension of tert-butyl 5-bromo-2-(tert-butoxycarbonyl)isoindoline (1.2 g, 4 mmol) and bis(pinacolato)diboron (2 g, 8 mmol) in DMSO (20 mL) was added AcOK (1.6 g, 16 mmol), followed by Pd(dppf)Cl2-CH2Cl2 (327 mg, 0.4 mmol) under N2 atmosphere. The reaction was heated at 90 C for 12 h, then cooled to rt and poured into EtOAc/H20 (300 mL/100 mL). The separatedorganic phase was washed with brine (100 mL), dried over anhydrous Na2S04, filtered and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (v/v) =20/1) to give the title compound as yellow oil (1 g, 73%). MS (ESI, pos. ion) m/z: 290.2 [M-56+l ; NMR (400 MHz, CDC13) delta (ppm): 7.68-7.74 (m, 2H), 7.23-7.30 (m, 1H), 4.64-4.70 (m, 4H), 1.53 (s, 9H), 1.36 (s, 12H).

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

Reference:
Patent; CALITOR SCIENCES, LLC; SUNSHINE LAKE PHARMA CO., LTD; XI, Ning; WANG, Ruyong; WANG, Liang; WO2014/89324; (2014); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Synthetic Route of 201940-08-1, 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. 201940-08-1 name is tert-Butyl 5-bromoisoindoline-2-carboxylate, 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.

Commercially available tert-butyl 5-bromoisoindoline-2-carboxylate (i.e., Matric Scientific, catalog 74109) (20 g, 0.0671 mol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(l,3,2- dioxaborolane) (17 g, 0.0671 mol), KAc (8.5 g, 0.087 mol) and PdCfedppf (1.8 g, 0.00221 mol) in 200 mL 1,4-dioxane was heated to 80C overnight. The mixture was cooled, water was added, the mixture was extacted with EA, dried and concentrated. The residue was purified by chromatography on silica gel to afford the title compound. 1HNMR (300MHz,DMSO)5: 1.2-1.3 (s, 12H), 1.4-1.5 (s, 9H), 4.5-4.6 (s, 4H), 7.2-7.3(m,lH), 7.5-7.6 (M,2H); LC-MS: m/z=246 (M+l-100)+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, tert-Butyl 5-bromoisoindoline-2-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MANDAL, Mihir; TANG, Haifeng; XIAO, Li; SU, Jing; LI, Guoqing; YANG, Shu-Wei; PAN, Weidong; TANG, Haiqun; DEJESUS, Reynalda; HICKS, Jacqueline; LOMBARDO, Matthew; CHU, Hong; HAGMANN, William; PASTERNAK, Alex; GU, Xin; JIANG, Jinlong; DONG, Shuzhi; DING, Fa-Xiang; LONDON, Clare; BISWAS, Dipshikha; YOUNG, Katherine; HUNTER, David, N.; ZHAO, Zhiqiang; YANG, Dexi; WO2015/112441; (2015); A1;,
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. 201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below. category: indolines-derivatives

In a microwave vessel, a solution of 5-bromo-l,3-dihydro-isoindole-2-carboxylic acid tert- butyl ester (1.5 equiv.), di(pinacolato)diborane (2.0 equiv.), potassium acetate (2.0 equiv.) in 1,4-dioxane (2.0 mL) is flushed with nitrogen. [l,l’-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.05 equiv.) was then added and the reaction mixture was flushed again with argon (and heated up to 900C for 20 hours until the reaction is complete on TLC. No purification was carried out.

The synthetic route of 201940-08-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GALAPAGOS NV; MENET, Christel Jeanne Marie; JOUANNIGOT, Nolwenn; BLANC, Javier; VAN ROMPAEY, Luc Juliaan Corina; FLETCHER, Stephen Robert; WO2010/10186; (2010); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Reference of 201940-08-1,Some common heterocyclic compound, 201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, molecular formula is C13H16BrNO2, 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.

0.69 ml of n-Butyl lithium (2.5M solution in hexane) was added dropwise to a stirred solution of 5- bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (429 mg; 1.44 mmol) in anhydrous THF (10 ml) at -78C under an atmosphere of nitrogen. The reaction was stirred for 50 minutes then 1-methyl-4-piperidone (212 mul; 1.2 equiv.) was added and stirred at -78C for a further 60 minutes then warmed to room temperature. The reaction was quenched with saturated ammonium chloride solution then extracted with EtOAc. The EtOAc layer was washed with saturated NaHCO3, brine, dried (MgSO4) and evaporated. Purification by flash column chromatography on SiO2, gradient elution from 0% to 10% 2M methanolic ammonia / DCM gave 111 mg of 5-(4-hydroxy-1-methyl- piperidin-4-yl)-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester as a colourless oil.

The synthetic route of 201940-08-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; WO2008/44029; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, A new synthetic method of this compound is introduced below., Computed Properties of C13H16BrNO2

5-Bromo-1 ,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (2.97 g, 10 mmol) was azeotropically dried by evaporation from toluene. Tris(dibenzylideneacetone)dipalladium (0) (228 mg, 0.25 mmol), 2-(di-tert-butylphosphino)biphenyl (149 mg, 0.50 mmol) and sodium tert-butoxide (1.34 g, 13.9 mmol) were added and the flask was purged with nitrogen. Toluene (25 mL) then N-methylpiperazine (1.33 mL, 12 mmol) were added and the mixture was heated to 8O0C for 2 hours. After allowing to cool to r.t. the mixture was diluted with ether, filtered through Celite and concentrated to give a residue that was purified by flash chromatography on silica (2M methanolic ammonia/dichloromethane, 1% to 3% gradient). This afforded the title compound as a brown solid (1.45g, 46%). 1H NMR (MeOH-d4) 7.15 (1 H, m), 6.94-6.88 (2H, m), 4.60-4.54 (4H, m), 3.20-3.17 (4H, m), 2.63-2.60 (4H, m), 2.34 (3H, s), 1.52 (9H, s). MS: [M+H]+ 318.

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; ASTEX THERAPEUTICS LIMITED; WO2008/44029; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

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. 201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., Formula: C13H16BrNO2

Tert-butyl-5-bromisoindoline-2-carboxylate (20.0 g, 67.09 mmol) was dissolved in Dioxane (200 ml.) and the solution was purged with Argon gas for 10 min. Bispinacalato diborane (34.07 g, 134.18 mmol), KOAc (26.34 g, 268.36 mmol) and Pd(PPh3)4 (7.75 g, 6.70 mmol) were added and the reaction mixture was stirred at 80C for 12 h. Reaction mixture was diluted with water, extracted with EtOAc (1 Ltr. X 2) twice The combined organic layers were washed with water (500 ml_), brine (300 ml_), dried over sodium sulphate and concentrated under vacuo. Crude compound was purified by Combiflash chromatography using 40 g Column and 10% EtOAc in n-Hexane to afford title compound as a White solid 23.0 g (99.30 %). Rf = 0.50 (10% EtOAc in n-Hexane); 1 H NMR (300 MHz, CDCI3): d 7.72-7.65 (m, 2H), 7.31 -7.20 (m, 1 H), 4.70-4.60 (m, 4H), 1 .40 (s, 9 H), 1 .37 (s, 12H).

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 201940-08-1.

Reference:
Patent; NOVARTIS AG; JIRICEK, Jan; NG, Shuyi Pearly; RAO, Srinivasa P S; (126 pag.)WO2019/244049; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Application of 201940-08-1,Some common heterocyclic compound, 201940-08-1, name is tert-Butyl 5-bromoisoindoline-2-carboxylate, molecular formula is C13H16BrNO2, 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.

Step 2: tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-isoindole-2-carboxylate A solution of tert-butyl 5-bromo-1,3-dihydro-2H-isoindole-2-carboxylate (0.80 mmol), bis(pinacolato)diboron (0.96 mmol) and potassium acetate (2.5 mmol) in DMF (4 mL) was degassed. To this solution was added PdCl2dppf (1:1 complex with DCM, 0.04 mmol). The reaction mixture was heated at 85 C. for 4 hr and then allowed to cool to rt and diluted with EtOAc. The solution was washed with water and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (10-30% EtOAc in hexane) to give tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-isoindole-2-carboxylate (0.57 mmol, 72%) as a white solid. LCMS: (FA) ES+346.

The synthetic route of 201940-08-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Millennium Pharmaceuticals, Inc.; US2008/171754; (2008); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem