Category: 4934-99-0

Electric Literature of 4934-99-0, 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. 4934-99-0 name is Methyl 3-hydroxycyclobutanecarboxylate, 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.

General procedure: To a flask containing alcohol (3 equiv.) in THF (0.1 – 0.5 M) at 0 C was added sodium hydride (3 equiv. 60% oil immersion). The resulting slurry was stirred 10 min and the alkyl bromide (1 equiv.) was added. The reaction mixture was allowed to reach rt and was stirred 2 h at which point NH4CI solution (saturated, 10 mL) was added followed by EtOAc (10 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (3 x 10 mL). The combined organic layers were dried over anhydrous MgSOr, filtered and concentrated under reduced pressure and purified employing either silica gel flash chromatography (0-> I 00% EtO Ac/hexanes) or reverse-phase preparatory HPLC (Phenomenex Luna 10 m C18, 100A,150 x 30 mm, 5 ->95% MeCN (0.1% formic acid) in H2O, 25 min, 60 mL/min) to afford the desired product.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 3-hydroxycyclobutanecarboxylate, and friends who are interested can also refer to it.

Reference:
Patent; DENALI THERAPEUTICS INC.; CRAIG, Robert A., II; DE VICENTE FIDALGO, Javier; ESTRADA, Anthony A.; FENG, Jianwen A.; FOX, Brian M.; LEXA, Katrina W.; OSIPOV, Maksim; SWEENEY, Zachary K.; THOTTUMKARA, Arun; (137 pag.)WO2019/183589; (2019); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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 4934-99-0 as follows. category: esters-buliding-blocks

Step 1: methyl 3-(l,3-dioxo-2,3-dihydro-lH-isoindol-2-yI)cyclobutane-l- carboxylate: into a 1000-mL round-bottom flask, was placed a solution of methyl 3- hydroxycyclobutane-l -carboxylate (10 g, 76.88 mmol, 1.00 eq.) in tetrahydrofuran (500 mL), 2,3-dihydro-l H-isoindole-l,3-dione (13.2 g, 89.7 mmol, 1.20 eq.), triphenyl phosphine (23.6 g, 90.0 mmol, 1.20 eq.). This was followed by the addition of DEAD (21 g, 120.6 mmol, 1.50 eq.) dropwise with stirring. The resulting solution was stirred for 3 h at room temperature. The reaction was then quenched by the addition of water. The resulting solution was extracted with 3×100 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1 : 1). This resulted in 6 g (30%) of methyl 3-(l ,3-dioxo-2,3- dihydro-l H-isoindol-2-yl)cyclobutane-l -carboxylate as a white solid. NMR (300MHz, CDC ): delta 7.85-7.81 (m, 2H), 7.75-7.70 (m, 2H), 5.09-5.03 (t, J= 8.7 Hz, 1 H), 3.32-3.29 (m, 1 H), 3.18-3.10 (m, 2H), 2.67-2.59 (m, 2H), 1.31 -1.24 (m, 3H). LC-MS: (M+H)+ = 260.

According to the analysis of related databases, 4934-99-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PROTEOSTASIS THERAPEUTICS, INC.; BASTOS, Cecilia, M.; MUNOZ, Benito; TAIT, Bradley; (96 pag.)WO2016/105468; (2016); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 4934-99-0, name is Methyl 3-hydroxycyclobutanecarboxylate, belongs to esters-buliding-blocks 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 4934-99-0, Recommanded Product: 4934-99-0

To a solution of methyl 3-hydroxycyclobutanecarboxylate AA28 (19.7 g, 152 mmol) in dichloromethane (200 mL) was added pyridine (90.0 g, 1.14 mol) , 4-dimethylaminopyridine (5.60 g, 45.6 mmol) and tosyl chloride (58.0 g, 303 mmol) at room temperature. After stirred at room temperature overnight, the mixture was poured water (200 mL) and extracted with ethyl ester (200 mL) twice. The combined organic layers were washed with 0.5 M hydrochloride aqueous solution (200 mL) , saturated sodium bicarbonate aqueous solution (200 mL) , water (200 mL) and brine (200 mL) , dried over Na2SO4 (s), filtered and the filtrate was concentrated under reduced pressure at room temperature to afford the title compound (42.7 g, 99 %yield) as yellow oil.1H NMR (300 MHz, CDCl3) delta 7.77 -7.73 (m, 2H) , 7.34 -7.26 (m, 2H) , 4.77 -4.64 (m, 1H) , 3.66 -3.59 (m, 3H) , 2.67 -2.54 (m, 1H) , 2.50 -2.37 (m, 7H) .

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, Methyl 3-hydroxycyclobutanecarboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; JANSSEN SCIENCES IRELAND UNLIMITED COMPANY; JOHNSON & JOHNSON (CHINA) INVESTMENT LTD.; JIANG, Yimin; WAN, Zhao-Kui; CHEUNG, Wing Shun; LIU, Qian; DENG, Gang; LIANG, Chao; (230 pag.)WO2019/214610; (2019); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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. 4934-99-0, name is Methyl 3-hydroxycyclobutanecarboxylate, A new synthetic method of this compound is introduced below., Recommanded Product: 4934-99-0

A solution of [1-[6-oxo-5-(trifluoromethyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1,6-dihydropyridazin-4-yl]pyrrolidin-3-yl]methyl 4-methylbenzene-1-sulfonate (1.09 g, 1.99 mmol, 1.00 equiv), methyl 3-hydroxycyclobutane-1-carboxylate (390 mg, 3.00 mmol, 1.50 equiv), sodium hydride (160 mg, 6.67 mmol, 2.00 equiv) in DMF (10 mL) was stirred for 6 h at 80 C. The resulting solution was quenched with 60 ml H2O, then the solution was extracted with EtOAc (3*60 mL) and the organic layers combined. The solution was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column eluting with EtOAc/petroleum ether (1:2) to afford 200 mg (20%) of the title compound as a white solid. LCMS (ESI, m/z): 506.23 [M+H]+

The synthetic route of 4934-99-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Ribon Therapeutics Inc.; Vasbinder, Melissa Marie; Schenkel, Laurie B.; Swinger, Kerren Kalai; Kuntz, Kevin Wayne; (410 pag.)US2019/330194; (2019); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Synthetic Route of 4934-99-0, A common heterocyclic compound, 4934-99-0, name is Methyl 3-hydroxycyclobutanecarboxylate, molecular formula is C6H10O3, 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.

At -10 , to 3-hydroxy-cyclobutane carboxylate (3.2g, 24.61mmol, 1eq.) In DCM (100mL) was added triethylamine(10.25mL, 73.83mmol, 3eq.) And methanesulfonyl chloride (2.29mL, 29.54mmol, 1.2eq.), The reaction was stirred at -10 3h. again60mL saturated ammonium chloride solution was added, the separated organic phase was washed with saturated sodium chloride solution (50mL x 2), dried over anhydrous sodium sulfate, and thenAfter concentration under reduced pressure, the residue was concentrated by silica gel column chromatography (eluent: PE / EtOAc (V / V) = 5/1) to give the title compound as a colorless oil (4.9 g of,95.7%).

The synthetic route of 4934-99-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; East Sunshine Pharmaceutical Co., Ltd. of Guangdong; Ren, Qingyun; Luo, Huichao; Tang, Changhua; Zhang, Jiancun; Zhang, Yingjun; (30 pag.)CN104447583; (2016); B;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 4934-99-0, 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. 4934-99-0 name is Methyl 3-hydroxycyclobutanecarboxylate, 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.

General procedure: To a flask containing alcohol (3 equiv.) in THF (0.1 – 0.5 M) at 0 C was added sodium hydride (3 equiv. 60% oil immersion). The resulting slurry was stirred 10 min and the alkyl bromide (1 equiv.) was added. The reaction mixture was allowed to reach rt and was stirred 2 h at which point NH4CI solution (saturated, 10 mL) was added followed by EtOAc (10 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (3 x 10 mL). The combined organic layers were dried over anhydrous MgSOr, filtered and concentrated under reduced pressure and purified employing either silica gel flash chromatography (0-> I 00% EtO Ac/hexanes) or reverse-phase preparatory HPLC (Phenomenex Luna 10 m C18, 100A,150 x 30 mm, 5 ->95% MeCN (0.1% formic acid) in H2O, 25 min, 60 mL/min) to afford the desired product.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 3-hydroxycyclobutanecarboxylate, and friends who are interested can also refer to it.

Reference:
Patent; DENALI THERAPEUTICS INC.; CRAIG, Robert A., II; DE VICENTE FIDALGO, Javier; ESTRADA, Anthony A.; FENG, Jianwen A.; FOX, Brian M.; LEXA, Katrina W.; OSIPOV, Maksim; SWEENEY, Zachary K.; THOTTUMKARA, Arun; (137 pag.)WO2019/183589; (2019); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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. 4934-99-0, name is Methyl 3-hydroxycyclobutanecarboxylate, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C6H10O3

10450] Step 1: To a nitrogen flushed vessel containing NaR (82 mg, 3.4 mmol), THF (6 mE) was added followed by the dropwise addition of methyl 3-hydroxycyclobutanecarboxy- late (0.360 mE, 3.4 mmol). The resulting suspension was allowed to stir at 0 C. for 35 mm. and then at RT for 45 mm. In a separate round bottom flask flushed with nitrogen, diisopropylamine (0.5 60 mE, 4 mmol) in THF (5 mE) was cooled to -78 C. before n-l3uEi (2.0 M in hexanes, 2 mE, 4 mmol) was added dropwise over 5 mm. The resulting solution wasallowed to stir at -78 C. for 30 mm. and then at 0 C. for 30 mm. The EDA thus generated was then added dropwise to the sodium alkoxide suspension at -78 C. Finally, ethyl iodide (0.320 mE, 4 mmol) was added and stirred at 0 C. for 15 mm and then at RT for 2.5 h. The crude mixture was quenched with sat. NH4C1 and extracted in ether. The combined organics were then washed further with brine, dried over Na2504, filtered and the filtrate concentrated in vacuo. Purification by way of column chromatography (5i02, 0-50% EtOAc/hexanes) afforded methyl 1 -ethyl-3-hydroxycyclobutanecar- boxylate. (277 mg, 51% yield).

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 4934-99-0.

Reference:
Patent; NOVIRA THERAPEUTICS, INC.; Chen, Austin; Bravo, Yalda; Stock, Nicholas; Pedram, Bijan; Jacintho, Jason; Clark, Ryan C.; (76 pag.)US2016/151375; (2016); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Application of 4934-99-0, 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. 4934-99-0, name is Methyl 3-hydroxycyclobutanecarboxylate, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of oxalyl chloride (5.25 mL, 60.0 mmol) in DCM (200 ml) at -78 C. was added DMSO (7.10 mL, 100 mmol). After 30 minutes, a solution of methyl 3-hydroxycyclobutanecarboxylate (6.51 g, 50 mmol) in methylene chloride (50 mL) was added. The mixture was stirred for 30 minutes at -78 C. and TEA (27.9 mL, 200 mmol) was then added. The mixture was allowed to warm to room temperature over 2 hours. To the reaction mixture was then added water and the layers separated. The organic phase was washed with water, dried over Na2SO4 and concentrated to give product (quantitative yield). 1H NMR (400 MHz, CDCl3): 3.14-3.32 (m, 3H) 3.32-3.46 (m, 2H) 3.73 (s, 3H)

The chemical industry reduces the impact on the environment during synthesis Methyl 3-hydroxycyclobutanecarboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Novartis AG; FU, Jiping; JIN, Xianming; KARUR, Subramanian; LAPOINTE, Guillaume; MADERA, Ann Marie; SWEENEY, Zachary Kevin; (45 pag.)US2016/166548; (2016); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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 4934-99-0 as follows. category: esters-buliding-blocks

Step 1: methyl 3-(l,3-dioxo-2,3-dihydro-lH-isoindol-2-yI)cyclobutane-l- carboxylate: into a 1000-mL round-bottom flask, was placed a solution of methyl 3- hydroxycyclobutane-l -carboxylate (10 g, 76.88 mmol, 1.00 eq.) in tetrahydrofuran (500 mL), 2,3-dihydro-l H-isoindole-l,3-dione (13.2 g, 89.7 mmol, 1.20 eq.), triphenyl phosphine (23.6 g, 90.0 mmol, 1.20 eq.). This was followed by the addition of DEAD (21 g, 120.6 mmol, 1.50 eq.) dropwise with stirring. The resulting solution was stirred for 3 h at room temperature. The reaction was then quenched by the addition of water. The resulting solution was extracted with 3×100 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1 : 1). This resulted in 6 g (30%) of methyl 3-(l ,3-dioxo-2,3- dihydro-l H-isoindol-2-yl)cyclobutane-l -carboxylate as a white solid. NMR (300MHz, CDC ): delta 7.85-7.81 (m, 2H), 7.75-7.70 (m, 2H), 5.09-5.03 (t, J= 8.7 Hz, 1 H), 3.32-3.29 (m, 1 H), 3.18-3.10 (m, 2H), 2.67-2.59 (m, 2H), 1.31 -1.24 (m, 3H). LC-MS: (M+H)+ = 260.

According to the analysis of related databases, 4934-99-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PROTEOSTASIS THERAPEUTICS, INC.; BASTOS, Cecilia, M.; MUNOZ, Benito; TAIT, Bradley; (96 pag.)WO2016/105468; (2016); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 4934-99-0, name is Methyl 3-hydroxycyclobutanecarboxylate, belongs to esters-buliding-blocks 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 4934-99-0, Quality Control of Methyl 3-hydroxycyclobutanecarboxylate

Methyl 3-(tert-butoxy)cyclobutane-1-carboxylate In a 30-mL round bottom flask purged and maintained with an inert atmosphere of nitrogen, methyl 3-hydroxycyclobutane-1-carboxylate (200 mg, 1.54 mmol, 1.00 equiv) and di-tert-butyl dicarbonate (771.4 mg, 3.53 mmol, 2.30 equiv) were mixed in dichloromethane (10 mL), to which was added magnesium perchlorate (34.3 mg, 0.15 mmol, 0.10 equiv) at room temperature. The resulting solution was then stirred for 16 h at 40 C. When the reaction was done, it was quenched with 10 mL water and the mixture was extracted with dichloromethane (3*10 mL). The organic layers were combined, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by prep-TLC eluting with ethyl acetate in petroleum ether (50%) to afford methyl 3-(tert-butoxy)cyclobutane-1-carboxylate (200 mg, 70%) as yellow oil. MS: m/z=187.1 [M+H]+.

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, Methyl 3-hydroxycyclobutanecarboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Merck Patent GmbH; GAILLARD, Pascale; SEENISAMY, Jeyaprakashnarayanan; LIU-BUJALSKI, Lesley; CALDWELL, Richard D.; POTNICK, Justin; QIU, Hui; NEAGU, Constantin; JONES, Reinaldo; WON, Annie Cho; GOUTOPOULOS, Andreas; SHERER, Brian A.; JOHNSON, Theresa L.; GARDBERG, Anna; (234 pag.)US2016/96834; (2016); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics