Month: November 2020

24398-88-7, 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 24398-88-7 as follows.

A mixture of 3- bromo-benzoic acid ethyl ester (229 mg, 1 mmol), 4-methylpiperidine ( 120 mg, 1 .2 mmol ), Pd2(dba)3 (25 mg ), BINAP (25 mg), and fBuONa ( 130 mg ) in toluene (6 mL) was heated at 90 C overnight. After the reaction was completed as indicated by TLC, the mixture was filtered and the filtrate was concentrated in vacuo. Ethyl acetate (50 mL) and aq. HC1 ( I , 20 mL) were then added. The aqueous portion was extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate, and filtered, concentrated, and purified by chromatography to give the title compound (76 mg, 3 1 %).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 24398-88-7, and friends who are interested can also refer to it.

Reference:
Patent; ARGUSINA INC.; LIAO, Jiayu; HONG, Yufeng; WANG, Yong; VON GELDERN, Thomas W.; ZHANG, Kanyin E.; WO2011/94890; (2011); A1;,
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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 701-83-7 as follows. 701-83-7

To 122 g (0.79 mol) of 3-fluorophenylacetate was added Aids (137 g, 1.03 mol) and theresulting mixture was heated at 160 C for 1.5 h then cooled at 0 C. HC1 IN was carefully addedfollowed by Et2O. The aqueous phase was extracted(2X) with Et2O and the combined organic phasewashed with brine, dried over Na2SO4 and evaporated to give the title compound.

According to the analysis of related databases, 701-83-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK FROSST CANADA & CO.; WO2004/108720; (2004); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

56525-63-4, Name is Methyl 3-chloro-4-methylbenzoate, 56525-63-4, belongs to esters-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows.

(2-Chloro-4-(methoxycarbonyl)benzyl)triphenylphosphonium bromideMethyl 3-chloro-4-methylbenzoate (2.20 g, 11.96 mmol) was dissolved in carbon tetrachloride (30 mL) and N-bromosuccinimide (2.10 g, 11.80 mmol) was added followed by a catalytic amount of benzoyl peroxide (25 mg). The reaction mixture was refluxed for 6h. (ca. 90% conversion). After cooling to room temperature, a precipitate was filtered. The filtrate was concentrated to give crude brominated intermediate (3.20 g), which was used for the next step without further purification.

Statistics shows that Methyl 3-chloro-4-methylbenzoate is playing an increasingly important role. we look forward to future research findings about 56525-63-4.

Reference:
Patent; REPLIGEN CORPORATION; JACQUES, Vincent; RUSCHE, James R.; PEET, Norton P.; SINGH, Jasbir; WO2012/118782; (2012); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

369-26-6, Adding some certain compound to certain chemical reactions, such as: 369-26-6, name is Methyl 3-amino-4-fluorobenzoate, 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 369-26-6.

To a solution of methyl 3-amino-4-fluorobenzoate (100 mg, 0.591 mmol) in DCM (3 ml) was added 4-(l-methylethyl)benzoyl chloride (162 mg, 0.887 mmol) and pyridine (96 mu, 1.18 mmol) at room temperature. The mixture was stirred for 1 h. 1 M HC1 and DCM were added and the phases were separated, the organic phase collected and the volatiles were removed in vacuo. The compound was purified by flash column chromatography. Yield: 135 mg (72percent); white solid. MS (ESI+) m/z 316 [M+H]+. HPLC purity: 99percent.

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 369-26-6.

Reference:
Patent; KANCERA AB; HAMMER, Kristin; JOeNSSON, Mattias; KRUeGER, Lars; (230 pag.)WO2017/108282; (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 619-42-1 as follows. 619-42-1

Synthesis methyl 4-(phenylamino)benzoate (Compound 17) Under argon atmosphere, a solution of methyl 4-bromobenzoate (3.5 g, 16.28 mmol), aniline (1.819 g, 19.53 mmol), palladium (II) acetate (218 mg, 0.97 mmol), rac-BINAP (506 mg, 0.81 mmol), and potassium carbonate (6.72 g, 48.62 mmol) in toluene (ca. 10 mL) was tightly capped in a 25 mL microwave vessel. The mixture was subjected to microwave irradiation at 160 C. for 2 h and then cooled to room temperature. The reaction mixture was diluted with DCM and filtered. The organic solvents were evaporated in vacuo, and the residue was suspended in methyl tert-butyl ether (150 mL). The organic phase was washed with saturated aqueous sodium bicarbonate, brine, dried (MgSO4), filtered and evaporated in vacuo. The obtained residue was purified by column chromatography (5% EtOAc in heptane to 60% EtOAc in heptane) to afford title compound 6 (3.55 g, 96% yield) as a pale green solid: mp 121-122 C.

According to the analysis of related databases, 619-42-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Diaz, Philippe; Diaz, Fanny; Petrov, Ravil Rashitovich; US2012/39804; (2012); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Some common heterocyclic compound, 105-53-3, name is Diethyl malonate, molecular formula is C7H12O4, 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. 105-53-3

To a solution of diethyl malonate (3.2 g, 20 mmol) and anhydrous potassium carbonate powder (6.9 g, 50 mmol) in DMF (50.0 mL) was added 1,2-dibromoethane (4.136 g, 22 mmol). After stirring for 2 hrs, catalytic amount of TBAI (0.738 g, 2.0 mmol) was added and the mixture was continued to stir at room temperature for 8 hrs. The reaction mixture was filtered and the solid was washed with diethyl ether 3 times. The filtrate was diluted with water (200 mL) and extracted with diethyl ether (75 mL*4). The combined organic phases were washed with 70 mL of brine, dried over Na2SO4 and concentrated in vacuo. The residue was chromatographed with a short alumina column (1: 10 (v/v) EtOAc / n-hexane) to afford the desired compound as yellow oil (3.3 g, 88.7 %). 1H NMR (400MHz, CDCl3): delta 1.27 (m, J=6.8Hz, 6H), 1.42 (m, 4H), 4.18 (m, 4H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 105-53-3, its application will become more common.

Reference:
Patent; Sunshine Lake Pharma Co., Ltd.; Xi, Ning; XI, Ning; (152 pag.)EP2408300; (2016); B1;,
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. 344-14-9, name is Dimethyl 2-fluoromalonate, A new synthetic method of this compound is introduced below., 344-14-9

General procedure: In a 50 mL two-necked flask containing dichloromethane (10 mL) were added the amine (17 mmol) followed by the aldehyde (15 mmol) and the resulting reaction mixture was allowed to stir at rt for 2 h, before the fluorinated dicarbonyl system (10 mmol) was added. The reaction mixture was stirred at rt for 16 h, evaporated and the residue dissolved in dichloromethane (20 mL), washed with distilled water (2¡Á20 mL), dried over magnesium sulfate and evaporated, to give the desired product. Further purification by distillation or column chromatography eluting from hexane/ethyl acetate was carried out when appropriate. Analytical and spectroscopic data for each individual compound are listed below. For NMR data only resonances of one diastereoisomer or conformer is given for clarity.

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:
Article; Lisse, Etienne; Sandford, Graham; Journal of Fluorine Chemistry; vol. 206; (2018); p. 117 – 124;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

3196-15-4, 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 3196-15-4 as follows.

Potassium carbonate (8.7 g, 63 mmol) was added to a solutionof 3-bromo-8-methylquinolin-6-ol (7, 5.0 g, 21 mmol) in 70 ml ofN,N-dimethylformamide. After the addition of methyl 2-bromobutyrate(7.1 g, 38 mmol), the reaction mixture was stirred for 16 h atroom temperature. Subsequently the mixture was filtered and thefiltrate was diluted with ethyl acetate. This organic phase waswashed with water and brine, dried over magnesium sulfate andevaporated under reduced pressure. The residue was purified bychromatography on silica gel, using ethyl acetate and cyclohexaneas eluents to yield 2-(3-bromo-8-methylquinolin-6-yloxy)-butyricacid methyl ester (8, 6.5 g, 19 mmol, 91%). 1H NMR (CDCl3):d = 1.04 (t, 3H, J = 7.3 Hz), 1.99 (q, 2H, J = 7.1 Hz), 2.68 (s, 3H),3.70 (s, 3H), 4.63 (t, 1H, J = 7.7 Hz), 6.65 (d, 1H, J = 2.3 Hz), 7.22(d, 1H, J = 2.2 Hz), 8.06 (d, 1H, J = 2.1 Hz), 8.68 (d, 1H, J = 2.1 Hz).LC-MS: Rt = 1.12 min; MS: m/z = 340 [M+1]+, 341 [M+2]+.

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

Reference:
Article; Lamberth, Clemens; Kessabi, Fiona Murphy; Beaudegnies, Renaud; Quaranta, Laura; Trah, Stephan; Berthon, Guillaume; Cederbaum, Fredrik; Knauf-Beiter, Gertrud; Grasso, Valeria; Bieri, Stephane; Corran, Andy; Thacker, Urvashi; Bioorganic and Medicinal Chemistry; vol. 22; 15; (2014); p. 3922 – 3930;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

653-92-9, 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. 653-92-9 name is Methyl 2-bromo-4-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.

Into a 250-mL round-bottom flask, was placed a solution of Example 1-i, i.e, 1- [[2-(4-chlorophenyl)-4,4-dimethylcyclohex- i-en-i -ylj methyljpiperazine (15.09 g, 47.32 mmol, 1.00 equiv) in DMA (150 mL), DIEA (12.9 g, 99.81 mmol, 2.00 equiv), methyl 2-bromo-4-fluorobenzoate (11.6 g, 49.78 mmol, 1.00 equiv). The resulting solution was stirred for 12 h at 100 degree. The reaction mixture was cooled to room temperature. The reaction was then quenched by the addition of 50 mL of water. The resulting solution was extracted with 3xiOO mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3xiOO mL of brine. The mixture was dried over anhydrous sodium sulfate, then filtered and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (0:1-1:5). This resulted in 7 g (crude) of methyl 2-bromo-4-(4-[[2- (4-chlorophenyl)-4,4-dimethylcyclohex- i-en-i -ylj methyljpiperazin- 1 -yl)benzoate as yellow oil. LC-MS: (ES, m/z): M+i=533, 531.

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

Reference:
Patent; NEWAVE PHARMACEUTICAL INC.; CHEN, Yi; LOU, Yan; (108 pag.)WO2019/40550; (2019); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Some common heterocyclic compound, 889858-12-2, name is tert-Butyl 4-bromo-2-fluorobenzoate, molecular formula is C11H12BrFO2, 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. 889858-12-2

To a 50 mL round-bottom flask was added Cs2CO3 (480 mg, 1.47 mmol, 3.00 equiv.), toluene (4 mL), tert-butyl 4-bromo-2-fluorobenzoate (162 mg, 0.59 mmol, 1.20 equiv.), 5-[[4- cyclopropyl-l-(2,6-dichlorophenyl)-1H-pyrazol-5-yl]methoxy]-3-ethyl-2- azabicyclo[2.2.1]heptane trifluoro acid acid salt 16b (200 mg, 0.49 mmol, 1.00 equiv.), Ruphos (82.3 mg, 0.20 equiv.), and Rupos preacatalyst (46 mg, 0.20 equiv.). The resulting mixture was heated at 110¡ãC overnight. After cooling to room temperature, the mixture was diluted with H2O (50 mL), extracted with ethyl acetate (100 mL x 2), and the combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by silica gel column chromatography eluting with ethyl acetate/hexane (1/3) to afford tert-butyl 4-(5-[[4-cyclopropyl-l-(2,6-dichlorophenyl)-1H-pyrazol-5- yl]methoxy]-3-ethyl-2-azabicyclo[2.2.1]heptan-2-yl)-2-fluorobenzoate 18a(180 mg, 61percent) as a yellow oil.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 889858-12-2, its application will become more common.

Reference:
Patent; ARDELYX, INC.; CHAO, Jianhua; (231 pag.)WO2019/55808; (2019); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics