Month: August 2021

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. 105-53-3, name is Diethyl malonate, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of Diethyl malonate

Reference Example 196 Ethyl 4-hydroxy-6-methylpyrimidine-5-carboxylate A mixture of diethyl malonate (4.8 mL), triethyl orthoacetate (17 mL), acetic anhydride (0.11 mL) and zinc chloride (1.2 g) was stirred at 140C. To the mixture was added acetic anhydride (0.11 mL) each after 30, 90 and 120 minutes, and then stirred at the same temperature overnight. The reaction mixture was cooled to room temperature, and the insoluble material was removed by filtration. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 4/1 – 7/3) to give diethyl 2-(1-ethoxyethylidene)malonate (5.02 g). To a solution of diethyl 2-(1-ethoxyethylidene)malonate (4.13 g) in ethanol (15 mL) were added formamidine hydrochloride (1.73 g) and a solution of potassium hydroxide (2.21 g) in water (7.5 mL), and the mixture was stirred at room temperature for 2 days. The reaction mixture was neutralized by adding acetic acid. To the mixture was added ethyl acetate (30 mL), and the mixture was stirred at room temperature for 30 minutes. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate – ethyl acetate/methanol = 9/1) to give the title compound (1.5 g).

According to the analysis of related databases, 105-53-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Kissei Pharmaceutical Co., Ltd.; EP2143724; (2010); A1;,
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Electric Literature of 57486-68-7,Some common heterocyclic compound, 57486-68-7, name is Methyl 2-chlorophenylacetate, molecular formula is C9H9ClO2, 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 31 1-(o-Chlorophenyl)-3-azabicyclo[3.1.0]hexane hydrochloride A stirred mixture of 36.9 g. of methyl o-chlorophenylacetate, 36.0 g. of N-bromosuccinimide, and 2 drops of 48% hydrobromic acid in 500 ml. of carbon tetrachloride is refluxed for 20 hours and then filtered through magnesium silicate. Evaporation under reduced pressure gives methyl alpha-bromo-o-chlorophenylacetate as a straw-colored liquid.

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

Reference:
Patent; American Cyanamid Company; US4435419; (1984); A;,
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Application of 59227-79-1, 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. 59227-79-1, name is Ethyl 4-(4-chlorophenoxy)butanoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

General procedure: Hydrazine hydrate (0.060 mol) was added to the solution of compounds 3a-h (0.045 mol) in ethanol (25 ml), and the reaction mixture was stirred at room temperature for 4 h. Reaction completion was monitored by thin-layer chromatography using hexane: ethyl acetate (2:1) as the mobile phase and allowed to stand overnight. Formed white crystals 4a-h were filtered, washed, and after drying recrystallized from ethanol to give 4a-h.

The synthetic route of Ethyl 4-(4-chlorophenoxy)butanoate has been constantly updated, and we look forward to future research findings.

Reference:
Article; Al-Ghorbani, Mohammed M. Abdullah; Indian Journal of Heterocyclic Chemistry; vol. 28; 3; (2018); p. 379 – 384;,
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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. 206551-41-9, name is Methyl 3-bromo-2-fluorobenzoate, A new synthetic method of this compound is introduced below., Computed Properties of C8H6BrFO2

In a 500 mL flask was placed 1 ,1-diotamethylethyl carbamate (6 03 g, 51 5 mmol), methyl 3-bromo-2-fluorobenzoate (10 g, 42 9 mmol), Pd2(dba)3 CHCI3 (0 89 g, 0 86 mmol), xantphos (1 49 g, 2 57 mmol) and cesium carbonate (16 8 g, 51 5 mmol) The flask was sealed with a rubber septum, placed under high vac, and toluene (200 mL) was added Three cycles of high vac/N2 were performed and the reaction 25 mixture was stirred at 90 C overnight The reaction was filtered through a pad of celite with EtOAc washing and concentrated To the residue was added DCM (200 mL) followed by TFA (50 mL, 649 mmol), and the mixture was stirred at rt for 1 h The volatiles were removed under reduced pressure and the residue was taken up in EtOAc and washed with saturated NaHCO3 and brine The organic layer was dried over sodium sulfate and stripped onto silica and column chromatographed on silica with 5% to 50% EtOAc Hexane to give 5 53 g (76%) of the title compound of Step B 1H-NMR (400 MHz, DMSO-d6) delta 6 92 – 7 01 (m, 3 H), 5 37 (s, 2 H), and 3 81 (s, 3 H) MS (ESI) 170 [M+H]+

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; GLAXOSMITHKLINE LLC; ADJABENG, George; BAUM, Erich; BIFULCO, Neil; DAVIS-WARD, Ronda, G.; DICKERSON, Scott, Howard; DONALDSON, Kelly, Horne; HORNBERGER, Keith; PETROV, Kimberly; RHEAULT, Tara, Renae; SAMMOND, Douglas, McCord; SCHAAF, Gregory, M.; STELLWAGEN, John; UEHLING, David, Edward; WATERSON, Alex, Gregory; WO2010/104899; (2010); A1;,
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Related Products of 3650-78-0,Some common heterocyclic compound, 3650-78-0, name is Methyl 3-(4-bromophenyl)acrylate, molecular formula is C10H9BrO2, 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.

Compound (7.5 g) obtained from step a above, pyridine-2-methoxy-5-boronic acid (9.48 g), tetrakistriphenylphosphinepalladium (0) (1.79 g) and potassium carbonate (12.83 g) were taken in dimethylformamide (60 mL) under nitrogen atmosphere. The reaction mixture was refluxed under nitrogen atmosphere for 6 hours. After cooling to room temperature, water was added and the reaction mixture was extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and the solvents were evaporated under reduced pressure. The crude product was purified by silica gel flash column chromatography using 20-30 % ethyl acetate in hexane to get the title compound (8.09 g).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 3-(4-bromophenyl)acrylate, its application will become more common.

Reference:
Patent; RANBAXY LABORATORIES LIMITED; WO2008/23336; (2008); A2;,
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Some common heterocyclic compound, 150529-73-0, name is Methyl 2-(3-bromophenyl)acetate, molecular formula is C9H9BrO2, 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. Safety of Methyl 2-(3-bromophenyl)acetate

A solution of the bromide from preparation 26 (15.0g, 65.0mmol), tributyltin methoxide (28.3ml, 98mmol), isopropenyl acetate (10.8ml, 98.0mmol), palladium(ll) acetate (750mg, 3.30mmol) and tri-orffto-tolylphosphine (2.0g, 6.5 mmol) were stirred together in toluene (75ml) at 100C under nitrogen for 5 hours. After cooling the reaction was diluted with ethyl acetate (1 50ml) and 4M aqueous potassium fluoride solution (90ml) and stirred for 15 minutes. The mixture was filtered through arbocel and the organic phase separated and reduced in vacua. The residue was purified by flash column chromatography silica gel eluting with a solvent gradient of diethyl ether:pentane:dichloromethane (0:100:0 changing to 25:75:0 then to 0:0:100, by volume) to give the title compound as a pale yellow oil (12.6g).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 150529-73-0, its application will become more common.

Reference:
Patent; PFIZER LIMITED; PFIZER INC.; WO2004/108675; (2004); A1;,
Ester – Wikipedia,
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Reference of 14273-90-6, 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. 14273-90-6, name is Methyl 6-bromohexanoate, This compound has unique chemical properties. The synthetic route is as follows.

To a suspension of hexane washed sodium hydride (216 mg, 4.32 mmol) in 5 mL of DMF was added a solution of (R,R)-3-hydroxyphenyl-2-propyl-N-formamido-N-alpha-methylbenzylamine (compound 5 of FIG. 6) (1.22 g, 4.32 mmol). After stirring for 30 min at room temperature, a solution of methyl 6-bromohexanoate (1.36 g, 6.48 mmol) in DMF (3 mL) was added and stirred overnight at room temperature. The reaction mixture was diluted with H2O (50 mL) and extracted with methylene chloride (3×10 mL). The combined organic fraction was washed with saturated sodium chloride solution and dried over Na2SO4. After removal of the solvent, the residue was purified on a silica gel column. Eluting with a solvent mixture (CH2Cl2:hexane:MeOH, 4:14:1) to give 1.68 g (95percent) of compound 6 of FIG. 6. 1H NMR (CDCl3) delta1.28 (dd, 3H), 1.53 (m, 2H), 1.58 (dd, 3H), 1.72 (m, 4H), 2.36 (m, 2H), 2.41 (m, 1H), 2.89 (m, 1H), 3.25 (m, 1H), 3.41 (t, 2H), 3.68 (s, 3H), 3.82 (q, 2H), 4.58, 6.07 (2 q, 1H), 6.17, 6.67 (2 s, 1H), 6.57, 6.40 (2d, 1H), 6.67 (dd, 1H), 7.05 (dd, 1H), 7.36 (m, 5H), 8.41, and 8.48 (two s, 1H). The sample was used in the next step without further characterization. (0217) A solution of the above formamide compound 6 of FIG. 6 (1.63 g) was treated with BH3.THF (10 mL) and stirred for 30 min when the excess of BH3 was decomposed with MeOH followed by dilute HCl. The reaction mixture was basified with dilute NH4OH and extracted with methylene chloride (3×25 mL). The organic fraction was dried over Na2SO4 and evaporated to dryness. The oily material was dissolved in MeOH (25 mL), and Pd/C (250 mg) was added. The mixture was heated to reflux with formic acid (3 mL in three portions) for an hour. The filtrate, obtained after removal of the catalyst, was evaporated and the resulting residue purified on a silica gel column. Elution with 10percent MeOH in methylene chloride gave 0.84 g (70percent overall in two steps) of a clear oil compound 8. 1H NMR (CDCl3) 1.06 (d, 3H), 1.50 (m, 2H), 1.71 (m, 2H), 1.80 (m, 2H), 2.33 (t, 2H), 2.41 (s, 3H), 3.67 (s, 3H), 3.95 (t, 2H), 6.75 (m, 3H), 7.19 (m, 1H). The sample was converted to HCl salt; mp 53-57° C. Elemental analysis: calcd. for C17H27NO3.HCl.0.75 H2O: C, 59.50; H, 8.50; N, 4.10. Found: C, 59.65; H, 8.45; N, 4.21

The chemical industry reduces the impact on the environment during synthesis Methyl 6-bromohexanoate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; The Board of Trustees of the University of Arkansas; Owens, Samuel M.; Carroll, Frank Ivy; Abraham, Philip; (77 pag.)US9303092; (2016); B2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Application of 25081-39-4, 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. 25081-39-4, name is Methyl 3,5-dimethylbenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

EXAMPLE 2 Preparation of methyl-3,5-bis(bromomethyl)-benzoate: A solution of methyl-3,5-dimethyl-benzoate (16.8 g, 0.10 mol) in carbon tetrachloride (150 ml) was treated with N-bromosuccinimide (35.6 g, 0.20 mmol), and benzoyl peroxide (500 mg, cat. amount), and heated to reflux. After 3 hours, the mixture was cooled to room temperature and filtered through a sintered glass funnel. The filtrate was concentrated under reduced pressure and recrystallized from diethyl ether/hexanes (1:1) to yield the product (18.0 g, 55% yield) as a granular white solid. mp 64-70 C. (lit. mp 65-69 C.); TLC (20% ethyl acetate/hexanes): Rf =0.65 (UV active, CAM stain)

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 3,5-dimethylbenzoate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; The Trustees of Columbia University in the City of New York; US5599926; (1997); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 711-01-3, 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 711-01-3 as follows.

Example-6; Charge Vitride (sodium dihydro-bis-methoxyethoxy alummate solution in toluene) reducing agent (200 gm) into a dry RBF at 25-35C under nitrogen atmosphere. Cool the Vitrideto 0C-5C. Slowly add toluene (300 ml) into RBF at 0C-5C. Prepare solution of XIII (100 gm) and toluene (200 ml) mixture; add this solution slowly to the reaction mass at 0C-5C. Maintain reaction mass for 10 min at 0C-5C. Raise the temperature to 25C-35C. Maintain the reaction mass for 1 hr at 25C-35C. Check TLC. After TLC complies, cool the reaction mass to 0C-5C. Slowly add saturated ammonium chloride solution to the reaction mass at 0C-5C. Maintain for 10-15 min. at 0C-5C. Filter the salts and wash with toluene (250 ml). Separate the organic layer and aqueous layer. Wash the toluene layer with sodium chloride solution (250ml x 2). Distill toluene out completely under vacuum at or below 70C. Residue weight: 95 gm. (Compound XIV).

According to the analysis of related databases, 711-01-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; APICORE, LLC; KOVI, Ravishanker; RAPOLE, Keshavrao; NAIK, Ashish; KANNAPAN, Jayaraman; MADALA, Muralikrishna; THAKOR, Sanjay, F.; WO2012/162507; (2012); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 206551-41-9, 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. 206551-41-9 name is Methyl 3-bromo-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.

Step 1: Methyl 3-((2-chloro-5-(1 ,4-dimethyl- 1H-1 ,2,3-triazol-5-yl)pyridin-3- yl)amino)-2-fluorobenzoateTo a 70 mL pressure vial containing 2-chloro-5-(1,4-dimethyl-1H-1,2,3-triazol-5- yl)pyridin-3-amine (Step 1 of Example 54, 500 mg, 2.24 mmol), methyl 3-bromo-2-fluorobenzoate (Oakwood, 781 mg, 3.35 mmol) and Cs2CO3 (728 mg, 2.24 mmol) in dioxane (10 mL) was added 1,1 ?-bis(diphenylphosphino)ferrocene (62.0 mg, 0.11 mmol), Pd(OAc)2 (85 mg, 0.38 mmol) and Xantphos (65 mg, 0.11 mmol). N2 was bubbled through the reaction mixture for 2 mm. The vial was sealed and heated to 100 °C for 24h. BrettPhos precatalyst (100 mg, 0.12 mmol) and additional methyl 3-bromo-2-fluorobenzoate (781 mg, 3.35 mmol) were added. N2 was bubbled through the reactionmixture for 2 mm, and then heating was continued at 110 °C for 24 h. Additional BrettPhos precatalyst (100 mg, 012 mmol) was added and stirring was continued at 120°C for 5 h. BrettPhos precatalyst (100 mg, 0.12 mmol) was again added and the reaction mixture was heated at 120 °C for 5 h. After cooling to room temperature, the mixturewas diluted with CHC13 and filtered through Celite® rinsing with CHC13. The filtrate was concentrated and purified using ISCO silica gel chromatography (40 g column, gradient from 0percent to 100percent EtOAc/CH2C12) to give the title compound (140 mg, 17percent) as a white solid. ?H NMR (400 MHz, CDC13) oe 7.90 (d, J=2.1 Hz, 1H), 7.74 (ddd, J=8.0, 6.5, 1.7 Hz, 1H), 7.52 – 7.44 (m, 1H), 7.24 (d, J=0.9 Hz, 1H), 7.17 (t, J2.0 Hz, 1H), 6.34 (s, 1H),3.97 (d, J=0.7 Hz, 6H), 2.32 (s, 3H); LCMS (M+H) = 376.3; HPLC RT = 2.23 mm(Column: Chromolith ODS S5 4.6 x 50 mm; Mobile Phase A: 10:90 MeOH:water with0.1percent TFA; Mobile Phase B: 90:10 MeOH :water with 0.1percent TFA; Temperature: 40 °C;Gradient: 0-100percent B over 4 mm; Flow: 4 mL/min).

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

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; NORRIS, Derek J.; DELUCCA, George V.; GAVAI, Ashvinikumar V.; QUESNELLE, Claude A.; GILL, Patrice; O’MALLEY, Daniel; VACCARO, Wayne; LEE, Francis Y.; DEBENEDETTO, Mikkel V.; DEGNAN, Andrew P.; FANG, Haiquan; HILL, Matthew D.; HUANG, Hong; SCHMITZ, William D.; STARRETT, JR, John E.; HAN, Wen-Ching; TOKARSKI, John S.; MANDAL, Sunil Kumar; WO2015/100282; (2015); A1;,
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