Author: Jessica.F

Reference of 56741-34-5, 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. 56741-34-5 name is Methyl 5-amino-2-fluorobenzoate, 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.

A mixture solution of 5-amino-2-fiuoro-benzoic acid methyl ester (26 g, 153.8 mmol), 3- bromo-benzaldehyde (28.5 g, 153.8 mmol) and -toluenesulfonic acid (590 mg, 3.2 mmol) in toluene (200 mL) was heated to reflux for 12 hours. Then the reaction mixture was cooled to room temperature. The solvent was removed in vacuo and the residue was washed with ether to afford 5- [(3-bromo-benzylidene)-amino] -2-fiuoro-benzoic acid methyl ester (51.7 g, quant.) as a pale-white solid: MS calcd. for Ci5HiiBrFlN02 337.16, obsd. (ESI+) [(M+H)+] 336.0 & 338.0.

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

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; CHEN, Li; FENG, Lichun; HUANG, Mengwei; LIU, Yongfu; WU, Guolong; WU, Jim, Zhen; ZHOU, Mingwei; WO2011/128251; (2011); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Related Products of 773134-11-5,Some common heterocyclic compound, 773134-11-5, name is Methyl 4-bromo-2,6-difluorobenzoate, molecular formula is C8H5BrF2O2, 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 solution of methyl 4-bromo-2,6-difluorobenzoate (22.5 g, 90 mmol) in N,N- dimethylformamide (100 mL) was added (2,4-dimethoxyphenyl)methanamine (16.49 g, 99 mmol) and K2C03 (18.58 g, 134 mmol) and the mixture was heated to 100 C and stirred overnight. The mixture was added to 50 mL water, extracted with ethyl acetate (30 mL x 3), dried over Na2S04 and evaporated to afford a brown oil. The oil was purified by column chromatography on silica gel (ethyl acetate/petroleum ether = 0 – 10%) affording methyl 4-bromo-2-((2,4-dimethoxybenzyl)amino)-6-fluorobenzoate (20 g, 45.2 mmol, 50 % yield) as a yellow solid. NMR (400 Hz, DMSO-d6 ) delta: ppm 7.85 (t, 1 H, J = 4.4 Hz), 7.16 (d, 1 H, J = 6.4 Hz), 6.755 (s, 1 H), 6.66 (d, 1 H, J = 8.8Hz), 6.60 (m, 1 H), 3.83 (s, 3 H), 3.81 (s, 3H), 4.13-3.94 (m, 3H), 3.48-3.50 (m, 1 H), 3.74 (s, 3H)

The synthetic route of 773134-11-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; JIN, Qi; POHLHAUS, Denise Teotico; SPLETSTOSER, Jared; (320 pag.)WO2017/98440; (2017); 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 4131-74-2 as follows. HPLC of Formula: C8H14O4S

Methanol (360 kg) was added to a glass lining kettle, stirred and cooled. The kettle was cooled to 0-5C. Methylamine (180 kg) was introduced within a period of 3-4 hours. After the introduction, the mixture was stirred for 10 minutes while keeping warm. The resultant product was discharged and sealed for storage.; The compound of formula II prepared according to Example 2 and a reacting mother liquid comprising methylamine (35%) were continuously added to the reaction kettle K1 (50 L) from the bottom at a speed of 1 kg per minute and 3 kg per minute, respectively. The resultant product was cooled to the temperature of 0-8C with stirring. The reaction solution overflowing the upper part (5/6 of the total height) of the reaction kettle K1 flowed into the reaction kettle K2 (50 L) from the bottom. The resultant mixture was cooled to the temperature of 0-8C with stirring. The reaction solution overflowing the upper part (5/6 of the total height) of the reaction kettle K2 flowed into the kettles K3 and K4 in the same manner. The reaction solution overflowing the upper part (5/6 of the total height) of the reaction kettle K4 alternately flowed into the centrifuges N1 and N2 having a diameter of 300 mm at a flowing speed of 4 kg/minute for a solid-liquid separation. The mother liquid entered the reaction kettle P (50 L) (in which liquid methylamine was continuously added to the kettle from the bottom at a speed of 0.26 kg/minute). The resultant product was subsequently pumped into the reaction kettle K1. The solid entered the reaction kettles Q1 and Q2 (50 L). The resultant mixture was washed with approximately equal mass of methanol and was subjected to a solid-liquid separation via the centrifuges R1 and R2 (300 mm), respectively. The solid was dried and entered the storage tank T. The experiment was carried out for 20 hours to give 498 kg of the compound of formula V (98.5% via chromatography analysis).

According to the analysis of related databases, 4131-74-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Beijing Tianqing Chemicals Co., Ltd.; EP2216331; (2010); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Electric Literature of 10203-58-4, These common heterocyclic compound, 10203-58-4, name is Diethyl isobutylmalonate, 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.

2-lsobuty3malonic acid diethyl ester (40. Og, 0.185 rnol) in DMF (50mL) was added dropwise to a stirred suspension of sodium hydride (60% in mineral oil, 8.0g, 0.33 mol) in 200 mL DMF (200mL) over 20 rain, at 0C under nitrogen. The mixture was stirred for 0.5 h at room temperature, cooled to 0 C and l,2,4-trifluoro-5-nitro-benzene (30. Og, 169.5 mmol) in DMF (150mL) was added dropwise. The resulting reaction mixture was stirred at room temperature for 16b, poured into ice water (2 OOmL) and extracted with EtOAc (3×1 OOmL). The combined organic phases were washed with water (3×1 OOmL), brine (lOOmL) and dried (MgS04).Evaporation of solvent under reduced pressure ga ve a brown oil which was purified by column chromatography over silica gel (Fle tane-EtOAc, gradient) to give 57.0 g (90%) of 2-(2,5- difluoro-4-nitropheny3)-2-isobuty3malonic acid diethyl ester as yellow oil.3FI NMR (300 MHz,CDCI3/TMS): delta 7.87 (dd, J = 12.3, 6.0 Flz, 1H), 7.79 (dd, J = 10.1 , 6.4 Hz, 1 H), 4.30-4.18 (m, 4H), 2.27 (d, J = 5.8 Hz, 2H), 1.60-1.50 (m, i l l ). 1.26 (t, J = 7.1 Hz, 6H), 0.82 (d, J = 7.0 Hz, 6H);3C NMR (75 MHz, CDClv’TMS): delta 168.2, 155.1 (d, Ja= 252.3 Hz), 150.9 (d, CF = 263.2 Hz), 135.7, 135. L 120.0 (dd,2JCF= 26.0,1= 4.0 Hz), 113.0 (d,2JC¥= 29.0 Hz), 62.3, 43.1 , 24.9, 23.8, 13.8.

Statistics shows that Diethyl isobutylmalonate is playing an increasingly important role. we look forward to future research findings about 10203-58-4.

Reference:
Patent; ENVIVO PHARMACEUTICALS, INC.; KOENIG, Gerhard; BLAIN, Jean-francois; WO2013/106328; (2013); 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 27741-65-7 as follows. Safety of Ethyl 2-cyclobutylideneacetate

In 40 mL of dry DCM ethyl 2-cyclobutylideneacetate (0.85 g, 6.07 mmol) was allowed to cool to -78 C. under nitrogen atmosphere. To this solution DIBAL-H (1M in toluene) (1.72 g, 12.1 mL, 12.1 mmol) was added dropwise. Reaction was monitored by TLC. When the starting material was consumed completely the reaction mixture was quenched with MeOH/H2O (1:1) (Rf=0.28, 20% ethyl acetate/n-hexane). DCM layer was separated and dried over sodium sulphate. DCM was removed under reduced pressure. Crude product was purified by column chromatography (silica gel 60-120 mesh, 0-20% ethyl acetate and n-hexane as eluent) afforded colorless oil. [0545] Yield: 0.5 g (84%) [0546] 1H NMR (400 MHz, CDCl3): delta 1.61 (br, 1H), 1.91-2.05 (m, 2H), 2.65-2.74 (m, 4H), 4.02 (d, J=7.2 Hz, 2H), 5.30-5.36 (m, 1H).

According to the analysis of related databases, 27741-65-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Cornell University; Coferon, Inc.; Purdue Research Foundation; Barany, Francis; Pingle, Maneesh; Bergstrom, Donald E.; Giardina, Sarah F.; Arnold, Lee Daniel; US2014/194383; (2014); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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. 609-12-1, name is Ethyl 2-bromo-3-methylbutanoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Safety of Ethyl 2-bromo-3-methylbutanoate

A solution of pyrazine-2-carbothioamide (1 g, 7.19 mmol) in ethanol (10 ml) was treated with ethyl 2-bromoisovalerate (2.25 g, 10.8 mmol), and pyridine (853 mg, 872 mul, 10.8 mmol) is combined to give a dark brown suspension. and heated to 100 C. for 6 hours in a sealed tube. The reaction mixture was cooled and concentrated to dryness under reduced pressure, and the resulting suspension is extracted with ethyl acetate (3*50 mL). The organic layers were combined, washed with saturated NaHCO3 (1*50 mL), saturated sodium chloride (2*20 mL). The organic layers were dried over MgSO4 and concentrated in vacuo to give 5-isopropyl-2-pyrazin-2-yl-thiazol-4-ol (260 mgs, 16%) which was used directly without further purification.

The synthetic route of 609-12-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Alam, Muzaffar; Du Bois, Daisy Joe; Hawley, Ronald Charles; Kennedy-Smith, Joshua; Minatti, Ana Elena; Palmer, Wylie Solang; Silva, Tania; Wilhelm, Robert Stephen; US2011/71150; (2011); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 85953-29-3, name is Methyl 2-chloro-4-fluorobenzoate, 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 85953-29-3, Safety of Methyl 2-chloro-4-fluorobenzoate

A mixture of 2-chloro-4-fluoro-benzoic acid methyl ester (3.51 g, 18.6 mmol), morpholine (1.95 mL, 22.3 mmol) and potassium carbonate (5.12 g, 37.1 mmol) in N-methylpyrrolidinone (20 mL) was stirred at 120C for 5h. The reaction was cooled, diluted with ethyl acetate and filtered through Celite. The filtrate was washed four times with water, once with brine, was dried (sodium sulfate) and evaporated. Purification by flash chromatography (SiO2) eluted with 2:8 ethyl acetate : hexanes to provid 2-chloro-4-morpholin-4-yl-benzoic acid methyl ester (3.08 g, 65% yield) as a white solid. . 1H-NMR (CDCl3, 500 MHz) 7.79 (d, 1H), 6.81 (d, 1H), 6.67 (dd, 1H), 3.81 (s, 3H), 3.78 (m, 4H), 3.20 (m, 4H) ppm; MS (FIA) 256.1 (M+H); HPLC (Method A) 3.275 min.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 2-chloro-4-fluorobenzoate, and friends who are interested can also refer to it.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2004/46120; (2004); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Application of 62638-06-6, 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. 62638-06-6, name is Dimethyl cyclohexane-1,3-dicarboxylate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

EXAMPLE 25; l,3-Dicarbomethoxybicyclo[3.2.1]octane; A cooled (-67C) solution of dry diisopropylamine (ll.OmL, 78 mmol) in anhydrous THF (60mL) in a 3-neck 500mL round bottom flask equipped with magnetic stirring, addition funnel, and gas inlet/thermometer was treated via syringe with 2.4N n-butyllithium/hexane (30mL, 72 mmol) at a rate to keep the pot temperature <-50C, warmed to 0C for 5 minutes, then recooled (-67 C). l,3-Dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidinone (DMPU, 36.3mL, 300 mmole, dried over molecular seives) was added dropwise so as to keep pot temp < -60 C, then a solution of dimethyl cyclohexane-l,3-dicarboxylate (12.01g, 60 mmol) in anhydrous THF (20mL) was likewise added dropwise. After lh at -67 C, a solution of l-bromo-2-chloroethane (12.05g, 84 mmol) in anhydrous THF (15mL) was added dropwise so as to keep pot temp <-50 C, and the mixture was warmed to room temperature over 1.5h and stirred at room temperature for 18h, then cooled on an ice bath and quenched with saturated aqueous ammonium chloride (50mL). The organic solvent was removed in vacuo and the aqueous residue was extracted with 9:1 hexane/ethyl acetate (150mL, lOOmL, 2X50mL). The combined organic extracts were washed with water (lOOmL), dried (MgS04), and concentrated in vacuo. The residue was dissolved in methylene chloride and passed through a pad of alumina in a 60mL fritted glass funnel (eluted with methylene chloride) to afford 15.36g (97% of theoretical) of a pale yellow oil which was essentially the desired intermediate with minor impurities.A solution of l-(2-chloroethyl)-l,3-dicarbomethoxycyclohexane (all of semi-purified from 60 mmol dimethyl cyclohexane-l,3-dicarboxylate) and DMPU (36.3mL, 300 mmol) in anhydrous THF (150mL) under nitrogen in a 500mL 3-neck flask equipped with magnetic stirring, addition funnel, and gas inlet/thermometer was cooled to -67C. Meanwhile, a cooled (-67C) solution of dry diisopropylamine (ll.OmL, 78 mmol) in anhydrous THF (75mL) under nitrogen was treated via syringe with 2.4N n-butyllithium/hexane (30mL, 72 mmol), the mixture was warmed to 0C for 5 min, then recooled (-67C). The LDA solution was cannulated in portions (~6) into the other solution at a rate to keep pot temperature <-60 C, then the mixture was stirred at -67 C for 30 min, warmed to room temperature over 1.5h, then stirred at room temperature for 18h,. cooled on an ice bath and quenched with saturated aqueous ammonium chloride (50mL). The organic solvent was removed in vacuo and the aqueous residue was extracted with 9:1 hexane/ethyl acetate (150mL, lOOmL, 2X50mL). The combined organic extracts were washed with water (lOOmL), dried (MgS04), and concentrated in vacuo. The residue was dissolved in methylene chloride and passed through a pad of alumina in a 60mL fritted glass funnel (eluted with methylene chloride) to afford crude subject material (9.52g) as a pale yellow oil. Chromatography on silica gel (~400cc) eluted with 40%, then 50% methylene chloride/hexane, then methylene chloride alone, then 10% ethyl acetate/methylene chloride afforded 8.32g (61% for two steps from dimethyl cyclohexane-l,3-dicarboxylate) purified subject material as a very pale yellow oil. [M+H]+=226.9. *H NMR (CDC13) 8 3.66 (s,6H), 2.20-2.30 (m,lH), 2.00-2.10 (m,2H), 1.70-1.80 (m,5H), 1.55-1.65 (m,4H). 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, Dimethyl cyclohexane-1,3-dicarboxylate, other downstream synthetic routes, hurry up and to see. Reference:
Patent; ROYALTY, Susan Marie; BURNS, James Ford; SCICINSKI, Jan Jozef; JAGDMANN, JR., Gunnar Erik; FOGLESONG, Robert James; GRIFFIN, Kellee Renee; DYAKONOV, Tatyana; MIDDLEMISS, David; WO2006/12395; (2006); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Application of 1459-96-7, These common heterocyclic compound, 1459-96-7, name is Dimethyl bicyclo[2.2.2]octane-1,4-dicarboxylate, 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.

Example 81 Bicyclo-[2.2.2]octane-1,4-dicarboxylic acid monomethyl ester (IV) A mixture of Bicyclo[2.2.2]octane-1,4-dicarboxylic acid dimethyl ester (III, Example 80, 20.4 g, 89.5 mmol), barium hydroxide octahydrate (14 g, 44.7 mmol) in methanol (160 ml) and water (40 ml) is stirred at 20-25 C. for 18 hour. The mixture is diluted with water (600 ml) and extracted with hexane (150 ml*2). The aqueous mixture is acidified (6 N hydrochloric acid) to pH=1-2 and extracted with chloroform (150 ml*2). The combined chloroform extracts are concentrated. The residue is dissolved in toluene, filtered and concentrated to give the title compound, mp=169-173 C.

The synthetic route of 1459-96-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Biogen, Inc.; US6649600; (2003); B1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 15964-79-1, 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. 15964-79-1 name is Methyl 2-(3,4-dimethoxyphenyl)acetate, 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 1.0 L three-necked round-bottomed flask was added 50 mL of THF and the reaction mixture was cooled to -78 C. Butyl lithium (BuLi, 1.6 M, 14.4 mL, 23 mmol) was added dropwise keeping the temperature below -70 C. Acetonitrile (1.3 mL, 25 mmol) in 30 mL of THF was added dropwise to the flask amidst stirring and cooling. After 2 hours (h) of stirring, (3,4-dimethoxyphenyl)acetic acid methyl ester (2.3 g, 11 mmol) was added to the resulting white colloidal mixture in the flask. The reaction mixture was stirred for a further 2 h, followed by the addition of saturated ammonium chloride solution (NH4Cl, 75 mL) at -78 C. The organic layer was separated, dried with sodium sulfate (Na2SO4), filtered to remove the drying agent and evaporated to dryness to give the crude product. This crude product was purified by silica gel column chromatography, eluting with 30-70% ethyl acetate (EtOAc) in hexanes to yield 4-(3,4-dimethoxyphenyl)-3-oxo-butyronitrile in the form of a solidifying amber oil, 1.8 g (75%).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 2-(3,4-dimethoxyphenyl)acetate, and friends who are interested can also refer to it.

Reference:
Patent; Cole, Derek Cecil; Boschelli, Diane Harris; Wang, Yanong Daniel; Asselin, Magda; Joseph-McCarthy, Diane Marie; Prashad, Amarnauth Shastrie; Wissner, Allan; Dushin, Russell; Wu, Biqi; Tumey, Lawrence Nathan; Niu, Chuan S.; Chen, Joan; US2007/287708; (2007); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics