Author: Jessica.F

These common heterocyclic compound, 89-91-8, name is Methyl 2,2-dimethoxyacetate, 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. Quality Control of Methyl 2,2-dimethoxyacetate

Cyclohexanone Compound 2a (1.37 g, 14.0 mMol) in THF (5 mL) was added dropwise to a solution of LHMDS (16.0 mL, 16.0 mMol) in anhydrous THF (25 mL) at -78 C. under a N2 atmosphere. The solution was stirred at -78 C. for about 1 hr. Methyl dimethoxyacetate Compound 11a (1.88 g, 14.0 mMol) in anhydrous THF (5 mL) was then added dropwise. The reaction mixture was stirred while warming to r.t. over a period of about 15 hrs, then the reaction was quenched with water (5 mL). The organic layer was diluted with EtOAc (100 mL) and washed with water and brine. The organic layer was separated and dried with anhydrous sodium sulfate, then filtered and concentrated in vacuo to yield a crude product as an oil. The oil was purified by flash chromatography (eluted with 10% EtOAc in hexane) to afford 2-(2,2-dimethoxy-acetyl)-cyclohexanone Compound 11b (1.82 g, 65%). Benzylhydrazine dihydrochloride Compound 11c (1.75 g, 9.00 mMol) and K2CO3 (1.51 g, 10.92 mMol) were added to a solution of Compound 11b (1.80 g, 9.10 mMol) in MeOH (50 mL) at 0 C. under a N2 atmosphere. The reaction mixture was stirred overnight while warming to r.t., then the reaction was quenched with water (20 mL). The organic layer was diluted with EtOAc (200 mL) and washed with water and brine. The organic layer was separated and dried with anhydrous sodium sulfate, then filtered and concentrated in vacuo to yield a crude product as an oil. The oil was purified by flash chromatography (eluted with 20% EtOAc in hexane) to afford 1-benzyl-3-dimethoxymethyl-4,5,6,7-tetrahydro-1H-indazole Compound 11d (1.80 g, 70%) as a colorless oil. 3N HCl (8 mL) was added to a solution of Compound 11d (1.70 g, 5.9 mMol) in acetone (50 mL) at 0 C. under a N2 atmosphere. The reaction mixture was stirred for 4 hrs while warming to r.t., then the reaction was quenched with water (20 mL), neutralized to pH 7 with K2CO3 and diluted with CH2Cl2 (100 mL). The organic layer was washed with water and brine, separated and dried with anhydrous sodium sulfate, then filtered and concentrated in vacuo to afford a 1-benzyl-4,5,6,7-tetrahydro-1H-indazole-3-carbaldehyde Compound 11e (1.35 g, 95%) as a colorless oil. Methanesulfonyl chloride Compound 11f1 (2.0 g, 17 mMol) and TEA (2.43 mL, 17.46 mMol) were added to a solution of (1R)-1-phenyl-ethylamine Compound 11f2 (1.75 g, 17.5 mMol) in CH2Cl2 (50 mL) at 0 C. under a N2 atmosphere. The mixture was stirred for 3 hrs while warming to r.t., then the reaction was quenched with water (5 mL). The organic layer was diluted with CH2Cl2 (100 mL) and then washed with water and brine. The organic layer was separated, dried with anhydrous sodium sulfate, then filtered and concentrated in vacuo to afford the corresponding N-(1-phenyl-ethyl)-methanesulfonamide Compound 11f3 as an oil. (Boc)2O (di-tert-butyldicarbonate) (4.57 g, 21.0 mMol) and DMAP (8 mg) were added to a solution of the methanesulfonamide Compound 11f3 in CH2Cl2 (10 mL) at 0 C. under a N2 atmosphere. The mixture was stirred overnight while warming to r.t., then the reaction was quenched with a saturated solution of NaHCO3 (sodium bicarbonate) (10 mL). The organic layer was diluted with CH2Cl2 (100 mL) and then washed with water and brine. The organic layer was separated, dried with anhydrous sodium sulfate, then filtered and concentrated in vacuo to yield a crude Boc-protected methanesulfonamide product. The product was purified by flash chromatography (eluted with 10% EtOAc in hexane) to afford (methylsulfonyl)[(1R)-1-phenyl-ethyl]-carbamic acid tert-butyl ester Compound 11f (3.89 g, 80%) as a colorless oil. Adapting a published procedure (Tozer M J, Woolford A J A and Linney I A, Synlett, 1998, 2, 186-188) to obtain the target compound, a 1M solution of KOtBu (potassium tert-butoxide) in THF (0.75 mL, 0.75 mMol) was added dropwise to a solution of the ester Compound 11f (0.070 g, 0.250 mMol) in anhydrous THF (5 mL) at -78 C. under a N2 atmosphere. After 45 min, Compound 11e (0.060 g, 0.250 mMol) diluted in THF (3 mL) was added dropwise. The solution was reacted over a 15 hr period while warming to ambient temperature. The reaction was quenched with water (5 mL). The organic layer was diluted with EtOAc (100 mL) and then washed with water and brine. The organic layer was separated and dried with anhydrous sodium sulfate, then filtered and concentrated in vacuo to yield a crude product. The product was purified by flash chromatography (eluted with 20% EtOAc in hexane) to give Compound 260 (0.079 g (75%), as a white solid. MS m/z 422 (MH+); 1H NMR (CDCl3, 400 MHz) delta 7.56 (d, J=15.5 Hz, 11H), 7.35-7.19 (m, 8H), 7.11-7.09 (m, 2H), 6.42 (d,J=15.5 Hz, 1H), 5.21 (s, 2H), 4.61-4.11 (m, 2H), 2.45-2.41 (m, 2H), 2.36-2.33 (m, 2H), 1.75-1.67 (m, 4H), 1.55 (d, J=6.5 Hz, 3H).

The synthetic route of Methyl 2,2-dimethoxyacetate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Lagu, Bharat; Liotta, Fina; Pan, Meng; Wachter, Michael P.; Xia, Mingde Xia; US2005/228034; (2005); 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 344-14-9 as follows. Computed Properties of C5H7FO4

A mixture of 2-fluoro-4-amidinopyridine hydrochloride (1.17 g, 6.662 mmol), dimethyl fluoromalonate (1 g, 6.662 mmol), DBU (3.35 mL, 22.4 mmol) and MeOH (50 mL) was stirred at room temperature overnight. The crude reaction mixture was evaporated under reduced pressure to yield a brown oil. A 2 N HC1 solution was cautiously added and the precipitate was collected by filtration, washed with water and dried in a vacuum oven to give the title compound (0.992 g, 66% yield). LCMS: RT 2.91 min, MI 225, Method (4LCMS1).

According to the analysis of related databases, 344-14-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; CARSWELL, Emma, L.; CHARLES, Mark, David; COCHI, Anne; DUGAN, Benjamin, J.; EKWURU, Chukuemeka, Tennyson; ELUSTONDO, Fred; FOWLER, Katherine, M.; LEROUX, Frederic, Georges, Marie; MONCK, Nathaniel, J.T.; OTT, Gregory, R.; ROFFEY, Jonathan, R.; SIDHU, Gurwinder; TREMAYNE, Neil; (305 pag.)WO2018/55402; (2018); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Synthetic Route of 1139-13-5,Some common heterocyclic compound, 1139-13-5, name is Diethyl cyclohexane-1,1-dicarboxylate, molecular formula is C12H20O4, 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 1. To a solution of compound 18-1 (4.0 g, 17.5 mmol) in EtOH (20 mL) was added 85% aqueous KOH solution (1.15 g, 17.5 mmol) at r.t. After the reaction mixture was stirred at 76 C for 3 h, it was concentrated and partitioned between EtOAc (15 mL) and H20 (25 mL). The aqueous phase was acidified with IN HC1 to pH = 3 and extracted with EtOAc (15 mL x 2). The organic layer was concentrated to give compound 18-2 as an oil (2.5 g, yield: 71.4%). ‘H NMR (400 MHz, CDC13) delta 4.20 – 4.15 (m, 2 H), 2.03 – 1.90 (m, 4 H), 1.56 – 1.47 (m, 6 H), 1.45 – 1.43 (t, 4.0 Hz, 3 H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Diethyl cyclohexane-1,1-dicarboxylate, its application will become more common.

Reference:
Patent; GENENTECH, INC.; THE UNIVERSITY OF AUCKLAND; LEE, Ho Huat; TERCEL, Moana; FLYGARE, John A.; GUNZNER-TOSTE, Janet; PILLOW, Thomas H.; SAFINA, Brian; STABEN, Leanna; VERMA, Vishal; WEI, BinQing; ZHAO, Guiling; WO2015/95227; (2015); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 150529-73-0,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.

A mixture of 121A (2.28 g, 10.0 mmol) and N-bromosuccinimide (1.96 g, 11.0 mmol) in carbon tetrachloride (20 mL) was deoxygenated with a flow of nitrogen for 5 min. 2,2′-Azobisisobutyronitrile (82 mg, 0.5 mmol) was added and the mixture was refluxed for 18 h. Hexanes was added to the cooled mixture, and the resulting solid was filtered and washed with hexanes. The filtrate was concentrated on a rotary evaporator and then chromatographed (silica gel, step gradient from 100% hexanes to 5% ethyl acetate in hexanes) to give 121B (1.3 g, 42%) as clear oil. LC-MS m/z: 309.1 (M+H)+.

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-(3-bromophenyl)acetate, its application will become more common.

Reference:
Patent; Bristol-Myers Squibb Company; US2007/3539; (2007); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 148547-19-7, A common heterocyclic compound, 148547-19-7, name is Methyl 4-bromo-3-methylbenzoate, molecular formula is C9H9BrO2, 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.

To a stirred solution of methyl 4-bromo-3-methylbenzoate (5g, 21.8 mmol) in dry 1 ,4- dioxane(100 ml_), were added dry Cs2CO3 (10.65 g, 32.7 mmol) and morpholine (2.3 g, 26 mmol). The mixture was degassed for 10 min. BINAP (0.67 g, 1.1 mmol) and palladium(ll)acetate (0.24 g, 1.1 mmol) were added under N2 and the resulting mixutre was refluxed for 15h. The reaction mixture was filtered through a pad of celite and the filtrate was evaporated. The crude product was purified by flash chromatography, affording the title compound as a yellow solid (4.3 g, 84%). 1H NMR (CDCI3, 400 MHz) delta 7.86-7.90 (m, 2H), 7.13-7.16 (d, 1 H), 3.98-4.0 (m, 4H), 3.91 (3H, s), 3.10-312 (m, 4H), 2.45 (3H, s). LC/MS (Method A): 236.0 (M+H)+. HPLC (Method B) Rt 2.24 min (Purity: 95.3%).

The synthetic route of 148547-19-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SERONO S.A.; WO2009/43889; (2009); A2;,
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. 1459-93-4, name is Dimethyl isophthalate, A new synthetic method of this compound is introduced below., COA of Formula: C10H10O4

In a 3-necked 500 mL round-bottomed flask equipped with a mechanical stirrer was placed dimethyl isophthalate (20.00 g, 0.103 mol, 1 eq.) dissolved in acetone (200 mL). To this mixture was added dropwise over 20 min a sln of NaOH (4.33 g, 0.108 mol, 1.05 eq.) in MeOH (40 mL). The resulting milky suspension was stirred at r.t. overnight. Then, another portion of NaOH (0.433 g, 0.011 mol, 0.1 eq.) was added into the reaction and the suspension was stirred for another 5 hours. The solvent was removed under vacuum and the white precipitate thus obtained was dissolved in water (400 mL). Concentrated HCl (15 mL) was added dropwise until pH~1. Then, the suspension was filtered; the collected precipitate was washed with water (4×100 mL) and dried under vacuum at 65C for 24 hours to give white solid 18.25 g. The obtained monomethyl isophthalate was used directly without further purification. In a 3 necked 500 mL round-bottomed flask equipped with a magnetic stirrer and a low temperature thermometer under a nitrogen atmosphere was placed monomethyl isophthalate (5.00 g, 0.027 mol, 1 eq.) dissolved in dry THF (125 mL). Then, this solution was placed in an ice-water bath and a solution of BH3?SMe2 (2M in THF, 70 mL, 0.14 mol, 5 eq.) was added dropwise slowly over 90 min to maintain the temperature in the solution below 7C. After another 15 min, the cooling bath was removed and the solution was allowed to reach ambient temperature. After 5 hours, the reaction was carefully quenched (strong gas evolution) with small pieces of ice while cooling in an ice-water bath. When the gas evolution ceased, brine (50 mL) was added and the resulting mixture was extracted with diethyl ether (3×100 mL). The combined organic extracts were washed with diluted bleach (50 mL, original solution 9.6% bleach diluted 10 times), brine (50 mL) and dried (MgSO4). The solvent was removed under vacuum to give an oil which contained a small amount of white precipitate. Diethyl ether (20 mL) was added and the solid was removed by filtration and washed with Et2O (2×10 mL). The filtrate was concentrated to yield a pale yellow oil (4.48 g). The crude oil was then purified by silica gel column chromatography (PE:EA, 4:1 to 7:3) to afford methyl 3-hydroxymethylbenzoate (2d) as colorless oil (3.77 g, 82%). Rf = 0.17 (EtOAc:PE = 1:4); 1H NMR (300 MHz, CDCl3), delta (ppm): 8.00 (s, 1H, HAr), 7.93 (dt, J = 7.7, 1.4 Hz, 1H, HAr), 7.61 – 7.51 (m, 1H, HAr), 7.40 (t, J = 7.7 Hz, 1H, HAr), 4.71 (s, 2H, OCH2), 3.89 (s, 3H, OMe).

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; Wang, Shuai; Lafont, Dominique; Rahkila, Jani; Picod, Benjamin; Leino, Reko; Vidal, Sebastien; Carbohydrate Research; vol. 372; (2013); p. 35 – 46;,
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. 24807-40-7, name is Methyl 3-(4-(benzyloxy)phenyl)propanoate, A new synthetic method of this compound is introduced below., Recommanded Product: 24807-40-7

To a solution of dimethyl methylphosphonate (1.16 g, 9.33 mmol) in THF (12.5 mL, 0.25 M) at -78 C was added nBuLi (3.9 mL, 9.33 mmol, 2.5 M in hexane). The mixture was stirred for 30 min after which a THF solution (2.5 mL) of ester 11 (750 mg, 3.10 mmol) was added slowly. The reaction mixture was warmed to RT and let stir for 1h, upon which time TLC indicated complete consumption of 11. The reaction mixture was quenched with saturated aqueous NH4Cl (5 mL). The mixture was diluted with H2O (10 mL) and extracted with EtOAc (4 x 25 mL). The combined organic layers were washed with H2O (50 mL), saturated aqueous NaCl (50 mL), dried over MgSO4, filtered, and concentrated in vacuo. Purification by FCC (EtOAc) yielded 12 (1.09 g, 3.01 mmol, 97%) as a clear oil. Data for 12: Rf 0.45 (1:1 Hexanes: EtOAc); IR (thin film) 3034, 2955, 1714, 1512, 1244 cm-1; 1H NMR (700 MHz, CDCl3) delta 7.44 (d, J = 7.5 Hz, 2 H), 7.39 (t, J = 7.6 Hz, 2 H), 7.34 (t, J = 8.6 Hz, 2 H), 6.91 (d, J = 8.6 Hz, 2 H), 5.05 (s, 2 H), 3.76 (d, J = 11.3 Hz, 6 H), 3.08 (d, J = 22.7 Hz, 2 H), 2.94 (t, J = 7.2 Hz, 2 H), 2.87 (t, J = 7.2 Hz, 2H); 13C NMR (176 MHz, CDCl3) delta 201.1, 157.2, 137.1, 132.9, 129.4, 128.6, 127.9, 127.5, 114.9, 70.0, 53.1 (d, J = 6.3 Hz), 45.8, 41.6 (d, J = 128.0 Hz), 28.6; HRMS (ESI) calcd for C19H24PO5 [M+H]: 363.1357, found 363.1361.

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; Salih, M. Quamar; Beaudry, Christopher M.; Tetrahedron Letters; vol. 58; 21; (2017); p. 2023 – 2025;,
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. 2216-92-4, name is N-Phenylglycine Ethyl Ester, This compound has unique chemical properties. The synthetic route is as follows., Safety of N-Phenylglycine Ethyl Ester

Example 71 Synthesis of 3-(2-naphthylsulfonyl)-1-(phenyl)-imidazolidin-2,4-dione (Compound 71): In a similar manner to Example 70, 470 mg (1.28 mmol; yield: 26.6%) of the title compound were obtained as white crystals from 860 mg (4.83 mmol) of ethyl N-phenylamino-acetate and 1.39 g (81%, 4.83 mmol) of 2-naphthalenesulfonyl isocyanate. Melting point: 208-210 C. PMR (delta ppm, DMSO-d6): 4.52(s,2H), 7.1-8.3(m,11H), 8.76(s,1H).

According to the analysis of related databases, 2216-92-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Suntory Limited; US5691335; (1997); A;,
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 541-16-2 as follows. Recommanded Product: 541-16-2

Compound 185a (3.15 g, 8.39 mmol) was dissolved in 50 mL of tetrahydrofuran,3.81 mL of tert-butoxycarboxylic anhydride (i.e., di-tert-butyl dicarbonate Boc2O, 16.78 mmol) and 100 mg of p-dimethylaminopyridine,Room temperature reaction 4h.The residue was purified by column chromatography, eluting with petroleum ether: ethyl acetate = 20: 1 (v / v) to give 3.18 g of compound 185b in 91% yield.

According to the analysis of related databases, 541-16-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Ocean University of China; Key Laboratory of Chemistry for Natural Products of Guizhou Province Chinese Academy of Sciences; Zhu, Weiming; Ma, Hongguang; Wang, Liping; Xu, Zhihong; Zhang, Yapeng; Wang, Yi; Liu, Peipei; (142 pag.)CN106083830; (2016); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

These common heterocyclic compound, 140-11-4, name is Benzyl acetate, 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. Application In Synthesis of Benzyl acetate

General procedure: Bioreactor cultures and biotransformations using E. coli JM109(pDTG601). Growth and biotransformation in the bioreactor usingE.coli JM109 (pDTG601) were carried out using a modification ofour previously published procedure.3b Thus, 5 mL of LB mediumsupplemented with ampicillin sodium salt (0.1 g/L) and glucose(5 g/L) were inoculated with a single colony of E. coli JM109(pDTG601), and grown overnight at 37 C and 150 rpm. Two500 mL shake-flasks containing 150 mL of MSB medium wereinoculated with 1 mL of the grown culture. These precultureflasks were placed in an orbital shaker at 37 C and 150 rpm, for12 hrs. Both entire cultures were used to inoculate the bioreactor(Sartorius Biostat A plus), charged with an initial volume of 2.5 L,and set to 500 rpm, 30 C, and air flow rate of 4L/min. The pHvalue was controlled automatically to 6.8 by addition of conc.ammonium hydroxide during the whole process. A pulse ofantifoam agents (Aldrich?s Antifoam Y: Silicone dispersion inwater 1:1) was added at the beginning of the run. At 6 h afterinoculation the dissolved oxygen value sharply increased(indicating carbon deprivation), whereupon a glucose fed-batchwas started by adding glucose (0.7 g/mL solution) from an initialrate of 0.08 mL/min to 0.54 mL/min in a 20 h period. When thebiomass concentration reached 15 g/L cdw, IPTG was added toinduce toluene dioxygenase expression (IPTG final concentrationin bioreactor of 10 mg/L), and the stirrer speed was set to900 rpm. After the culture reached the stationary phase (c.a.26 h, 50 g/L cdw aprox), glucose feeding was decreased to0.25 mL/min and substrate addition was started. A solution of thecorresponding substrate in liquid paraffin (0.5 M) was added at aflow rate of 20 mL/min using a peristaltic pump. After thebiotransformation was completed, the pH of the medium in thebioreactor was adjusted to 7.5. The culture broth was centrifugedat 7000 rpm and 4 C for 30 min, the supernatant was collectedand the cell pellet properly disposed. Centrifugation led to theseparation of the liquid paraffin (which contains no detectableamounts products) from the aqueous phase. The latter wasproperly lyophilized overnight to obtain a dry powder, whichwas extracted several times with ethyl acetate until no morediols were detected by TLC. The solvent was evaporated to affordthe corresponding diol, which was washed several times withhexanes to remove the liquid paraffin traces.

The synthetic route of Benzyl acetate has been constantly updated, and we look forward to future research findings.

Reference:
Article; Pazos, Mariana; Martinez, Sebastian; Vila, Maria Agustina; Rodriguez, Paola; Veiga, Nicolas; Seoane, Gustavo; Carrera, Ignacio; Tetrahedron Asymmetry; vol. 26; 24; (2015); p. 1436 – 1447;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics