Month: October 2020

Some common heterocyclic compound, 252881-74-6, name is tert-Butyl 3-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)propanoate, molecular formula is C13H27NO5, 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. 252881-74-6

In a solution of tert-butyl 3- (2- (2- (2-aminoethoxy) ethoxy) ethoxy) propanoate (6.00 g, 21.64 mmol) and 3, 3′- ( (oxybis (ethane-2, 1-diyl) ) bis (oxy) ) dipropanoic acid (21.01 g, 84.00 mmol) in DMA (200 ml) were added EDC (18.00 g, 93.75 mmol) and DIPEA (5.00 g, 38.75 mmol) . The mixture was stirred overnight, then concentrated and purified by SiO 2 column chromatography (MeOH: CH 2Cl 2 = 1: 12 to 1: 5) to give the title compound as a white oil (9.15 g, 86%yield) . ESI m/z: calcd for C 23H 44NO 11 [M+H] +: 510.28, found: 510.55.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 252881-74-6, its application will become more common.

Reference:
Patent; HANGZHOU DAC BIOTECH CO., LTD; ZHAO, Robert Yongxin; ZHUO, Xiaotao; YANG, Qingliang; ZHAO, Linyao; HUANG, Yuanyuan; YE, Hangbo; YANG, Chengyu; LEI, Jun; GAI, Shun; GUO, Huihui; JIA, Junxiang; BAI, Lu; XIE, Hongsheng; ZHOU, Xiaomai; GUO, Zhixiang; LI, Wenjun; CAO, Mingjun; ZHENG, Jun; YE, Zhichang; YANG, Yanlei; (325 pag.)WO2020/6722; (2020); 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. 139102-34-4, name is Methyl 4-bromo-2-methoxybenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. 139102-34-4

1.936 kg (6.22 mol) of a 65% Red-Al solution in toluene were charged with 1.25 l of toluene at -5 C. To this solution was added 0.66 kg (6.59 mol) of 1-methylpiperazine, which was rinsed in with 150 ml of toluene, keeping the temperature between -7 and -5 C. The mixture was then left to stir at 0 C. for 30 minutes. This solution was then added to a solution of 1.261 kg (5.147 mol) of methyl 4-bromo-2-methoxybenzoate (XV), dissolved in 4 l of toluene, keeping the temperature at -8 to 0 C. After rinsing in twice with 0.7 l of toluene, the mixture was then stirred at 0 C. for 1.5 hours. For the work-up, the solution was added to cold aqueous sulphuric acid at 0 C. (12.5 l of water+1.4 kg of conc. sulphuric acid). The temperature should increase at maximum to 10 C. (slow addition). The pH was adjusted to pH 1, if necessary, by addition of further sulphuric acid. The organic phase was separated off and the aqueous phase was extracted with 7.6 l of toluene. The combined organic phases were washed with 5.1 l of water and then substantially concentrated and the residue taken up in 10 l of DMF. The solution was again concentrated to a volume of about 5 l. Determination of the content by evaporation of a portion resulted in a converted yield of 1.041 kg (94.1% of theory). The solution was used directly in the subsequent stage. HPLC method A: RT about 12.1 mm. MS (Elpos): mlz=162 [M+H]. 1H NMR (CDC13, 400MHz): oe=3.93 (3H, s), 7.17 (2H, m), 7.68 (1H, d), 10.40 (1H, s)

The synthetic route of 139102-34-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; PLATZEK, Johannes; (30 pag.)US2018/244670; (2018); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

24398-88-7, 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. 24398-88-7, name is Ethyl 3-bromobenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

A mixture of ethyl-3-bromobenzoate (3.0 g, 13 mmol), [3-(hydroxymethyl)- phenyl]boronic acid (3.0 g, 20 mmol), PdCl2(PPh3)2 (0.46 g, 0.66 mmol), K2CO3 (3.6 g, 26 mmol), methanol (4 mL), and toluene (36 mL) was heated at 80 0C for 18 h under N2 and then allowed to cool to rt. The reaction mixture was filtered through Celite and then poured into a mixture of ethyl acetate and brine. The two layers were separated and the aqueous layer was extracted with ethyl acetate (x 3). The organic extracts were dried (Na2SO4), filtered, concentrated and purified by silica gel chromatography to give ethyl 3′- (hydroxymethyl)biphenyl-3-carboxylate as an orange oil. A solution Of CBr4 (5.8 g, 17 mmol) and CH2Cl2 (20 mL) was added dropwise to a solution of the above alcohol, PPh3 (4.6 g, 18 mmol), and CH2Cl2 (50 mL) at 0 0C under N2. The reaction was allowed to warm to rt, maintained for 2 h, concentrated, and purified by silica gel chromatography to give ethyl 3′- (bromomethyl)biphenyl-3-carboxylate as a clear oil. Ethyl 3′-(bromomethyl)biphenyl-3- carboxylate was used to alkylate l-(2,2-dimethylpropyl)-4-propyl-lH-indol-5-ol following the procedure outlined in example 1. A mixture of the above indole (0.66 g, 1.4 mmol), 1 N LiOH (8 mL), and TEtaF (8 mL) was heated at 40 0C for 2 d and then cooled to 0 C- acetone can used in place of TEtaF if faster reaction rates are desired. The reaction was acidified to pEta = 1 with cone. HCl and extracted with ethyl acetate (x 3). The organic extracts were dried (Na2SO4), filtered, concentrated and purified by silica gel chromatography to give a yellow oil. 1H NMR (CDCl3, 500 MHz) delta 8.39 (s, IH), 8.11 (d, IH), 7.85 (d, IH), 7.76 (s, IH), 7.59- 7.48 (m, 4H), 7.12 (d, IH), 7.05 (d, IH), 6.96 (d, IH), 6.46 (d, IH), 5.16 (s, 2H), 3.84 (s, 2H), 2.95 (t, 2H), 1.76 (m, 2H), 1.01 (t, 3H), 0.99 (s, 9H). MS (ESI): 456 (M+H).

The synthetic route of 24398-88-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK & CO., INC.; WO2006/91496; (2006); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

680-65-9, A common compound: 680-65-9, name is Diethyl difluoromalonate, belongs to esters-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

5 g (1.0 eq., 25.49 mmol) of the compound 37 was dissolved in 40 mL of methanol, and 30 mL of methanol solution of sodium hydroxide (1.43 g (1.0 eq., 25.49 mmol)) was added dropwise thereto. It was then stirred for 3 hours at room temperature. After confirming by TLC the disappearance of the reacting materials, benzyl amine (8.4 mL (3.0 eq., 76.47 mmol)) was added and stirred overnight at 55 C. The reaction solution was concentrated under reduced pressure by using an evaporator, and the precipitated solids were added with diethyl ether followed by washing and filtering. The washed solids were dissolved in 1 M HCl. Then, liquid fractionation extraction was performed 3 times using ethyl acetate. The collected organic layer was washed with a saturated aqueous solution of NaCl. After drying over magnesium sulfate, it was concentrated under reduced pressure by using an evaporator in water bath at 40 C. to obtain the residues (compound 39). It was directly subjected to the following reducing reaction.

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, Diethyl difluoromalonate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Seikagaku Corporation; Miyamoto, Kenji; Yasuda, Yosuke; Takeuchi, Hisayuki; Yoshioka, Keiji; (69 pag.)US2016/151506; (2016); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

1459-96-7, A common compound: 1459-96-7, name is Dimethyl bicyclo[2.2.2]octane-1,4-dicarboxylate, belongs to esters-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

Step C. A mixture of the title compound from Step B above (20 g) and KOH (5.5 g) in MeOH/H2O (10:1, 106 mL) was heated to reflux overnight, cooled to room temperature and concentrated. The residue was diluted with EtOAc and extracted with IN aqueous NaOH (2 x 10O mL). The organic phase was dried (MgSO4), filtered and concentrated to give the starting material as a white solid. The combined aqueous phases were adjusted with 2N aqueous HCl to pH 1-2 and extracted with EtOAc (4 x 250 mL). The combined turbid organic phases were filtered through a fluted filter, washed with saturated aqueous NaCl, dried (MgSO4), filtered and concentrated to give the title compound as a colorless solid (13.1 g, 70%). [MH]+ = 213.

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 bicyclo[2.2.2]octane-1,4-dicarboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ALANTOS PHARMACEUTICALS HOLDING, INC.; WO2008/63671; (2008); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

581065-95-4, 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. 581065-95-4 name is tert-Butyl 1-amino-3,6,9,12-tetraoxapentadecan-15-oate, 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.

BOP (0.3 g, 0.73 mmol) and DIPEA (0.26 mL, 1.52 mmol) were added to a suspension of 11 (0.1 g, 0.15 mmol) and amino-CH2CH2-POE4-CO2tBu (0.21 g, 0.67 mmol) in DMF (6 mL). The reaction mixture was stirred for 96 hours at room temperature, and the solvent was evaporated under reduced pressure. The residue was dissolved in CH2Cl2, washed with brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by size exclusion chromatography (Sephadex, LH20. GE Healthcare, CH2Cl2/MeOH 50/50) to give compound 12 (88%) in the form of a yellow oil. (0287) 1H NMR (300 MHz, CDCl3) delta (ppm) 1.45 (s, 36H, 4 tBu), 2.24 (bs., 1H, H alkyne), 2.30-3.00 (m, 24H, 4 CH2COOtBu, 6 CH2CONH PAMAM, 2 CONHCH2CH2NHCO), 3.10-3.71 (m, 88H, CH2N and NCH2 PAMAM, CH2O, 4 CONHCH2CH2O), 3.79 (m, 2H, CH2 alkyne), 5.30 (m, 2H, NH), 7.20 (m, 4H, NH); 13C NMR (75 MHz, CDCl1) delta (ppm) 173.2, 170.9, 170.7, 80.3, 73.9, 70.4, 70.3, 70.2, 70.0, 69.9, 69.2, 52.7, 50.5, 49.0, 39.9, 39.1, 36.0, 33.1, 27.9.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, tert-Butyl 1-amino-3,6,9,12-tetraoxapentadecan-15-oate, and friends who are interested can also refer to it.

Reference:
Patent; UNIVERSITE DE STRASBOURG; UNIVERSITE CLAUDE BERNARD LYON 1; HOSPICES CIVILS DE LYON; CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE -CNRS; FELDER-FLESCH, Delphine; BILLOTEY, Claire; PARAT, Audrey; GAROFALO, Antonio; KRYZA, David; JANIER, Marc; (138 pag.)US2016/221992; (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 99548-54-6 as follows. 99548-54-6

A solution of methyl 3-bromo-2-methylbenzoate (from for example AstaTech, 24.35 g, 106 mmol) in benzene (300 mL) was treated with N-bromosuccinimide (22.7 g, 128 mmol) followed by benzoyl peroxide, 95% (1.3 g, 5.35 mmol). The reaction mixture was flushed with nitrogen and kept under nitrogen. The reaction mixture was heated at 80C for 2 days. The reaction mixture was concentrated under reduced pressure and treated with hexanes (200 mL). The resulting solids were filtered off, washed with hexanes then with 25% EtOAc / hexanes. The filtrate was concentrated under reduced pressure and the residue was absorbed directly onto silica gel. The product was purified by chromatography (ISCOCombiflash, 330 g, 200 ml/min, 0-8.7% EtOAc / Hexanes over 30 minutes) to yield the title compound (32.4 g, 105 mmol, 99% yield) as an orange liquid. LC/MS: RT= 1.13 min, m/z = 226.8/228.9.

According to the analysis of related databases, 99548-54-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; HARLING, John David; NEIPP, Christopher E.; PENDRAK, Israil; SMITH, Ian Edward David; TERRELL, Lamont Roscoe; YOUNGMAN, Mark; (120 pag.)WO2017/46036; (2017); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

369-26-6, name is Methyl 3-amino-4-fluorobenzoate, 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. 369-26-6

Step 1 : 3-Amino-N-(2-tert-butoxyethyl)-4-fluorobenzamide A mixture comprising 2-tert-butoxyethanamine (1 .2 g, 5.12 mmol, 50percentw/w) and methyl 3-amino-4-fluorobenzoate (0.866 g, 5.12 mmol) in THF (10 ml) was treated with TBD (0.713 g, 5.12 mmol) and heated at 90 ¡ãC for 16 hrs. After cooling to RT, the solvent was removed in vacuo and the residue was partitioned between water and EtOAc. The organic portion was separated and washed with 10percent aq citric acid (x 2), NaHC03(sat. aq), brine, dried (MgS04) and concentrated in vacuo. Purification of the crude product by chromatography on silica eluting with 0-100percent EtOAc in iso- hexane afforded the title compound as a clear oil;LC-MS: Rt 1.09 mins; MS m/z 255 [M+H]+; Method 2minl_C_v003

Statistics shows that 369-26-6 is playing an increasingly important role. we look forward to future research findings about Methyl 3-amino-4-fluorobenzoate.

Reference:
Patent; NOVARTIS AG; IRM LLC; BRUCE, Ian; CHAMOIN, Sylvie; COLLINGWOOD, Stephen Paul; FURET, Pascal; FURMINGER, Vikki; LEWIS, Sarah; LOREN, Jon Christopher; MOLTENI, Valentina; SAUNDERS, Alex Michael; SHAW, Duncan; SVIRIDENKO, Lilya; THOMSON, Christopher; YEH, Vince; JANUS, Diana; WEST, Ryan; WO2013/30802; (2013); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

3196-15-4, These common heterocyclic compound, 3196-15-4, name is Methyl 2-bromobutyrate, 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 1Preparation of methyl 2-(6-methoxy-lH-inden-3-yl) butanoateAn oven dried 5 -L four-necked round -bottomed flask was fitted with a thermometer, a condenser, an addition funnel, and a mechanical stirrer. Under Ar protection, a suspension of 5-methoxy-l-indanone (80.0 g, 494 mmol), Zn powder (Lancaster, 56.2 g, 865 mmol) in 2 L anhydrous TEtaF was stirred at 6O0C (internal temperature), while a solution of methyl bromobutyrate (134.1 g, 74] mmoi) in 400 inL anhydrous TEtaF was added slowly through an addition funnel After completion of the addition, the reaction mixture was stirred at 6O0C (internal temperature) for 1 hour. The reaction was followed by TLC analysis of aliquots following IN aqueous HCl work-up. After the reaction was completed, it was cooled in an ice-water bath followed by slow addition of 3 L of IN HCl solution. The pot temperature was kept below 2O0C. The mixture was then extracted with 1 L EtOAc. The organic layer was washed with water until pH 6.0-7.0, then saturated NaCl solution, and dried over Na2SO4, The product (127 g, >;99%), a yellow oil, was obtained after solvent removal and drying under vacuum. 1H NMR (DMSO-t,) delta 7.28(d, IH), 7.05(d, IH), 6.82(dd, IH), 6.22(s, IH), 3.72(s, 3H), 3.60(m, IH), 3.58(s, 3H), 3.28(s, 2H), 1.95(m, IH), 1.80(m, IH), 0.88(t, 3H).

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 3196-15-4.

Reference:
Patent; DARA BIOSCIENCES, INC.; DELMEDICO, Mary Katherine; WO2010/141696; (2010); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

59247-47-1, These common heterocyclic compound, 59247-47-1, name is tert-Butyl 4-bromobenzoate, 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 50-mL round-bottom flask was added (1 S,4S,.5R)-.5-[[5-cyclopropyl-3-(2,6-dichlorophenyl)- L2-oxazol-4-yl]methoxy]-2-azabicyclo[2.2.1 ]heptane 12d (800 mg, 2.11mmol, 1.0 equiv.), tert-buty 4-bromobenzoate 52b (650 mg, 2.53 mmol, 1.20 equiv.),Pd2(dba)3 (190 mg, 0.21 mmol, 0.10 equiv.), BINAP (130 mg, 0.21 mmol, 0.10 equiv),Cs2C01 (960 mg, 2.9.5 mmoL 1.40 equiv.), and toluene (.5 mL) and the resulting mixture was20 stirred at 110 ¡ãC overnight. After cooling to room temperature, l 00 mL of I-hO v.¡¤as addedand the aqueous mixture was extracted with ethyl acetate (l 00 mL x 2). Tiw combinedorganic extracts were washed with brine (100 mL x 2), dried over anbydrous sodium sulfate,filtered, and concentrated under reduced pressure. The residue was purified by silica gelcolumn chromatography eluting vvith ethyl acetate/petroleum ether (1 :6) to give 0.55 g (4Tpercent)25 of tert-buiyl 4-[(1 S,4S,5R)-.5-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-l ,2-oxazol-4-yl]methoxy ]-2-azabicyclo[2.2.1 ]heptan-2-yl]benzoate 52c as a light green solid.

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 59247-47-1.

Reference:
Patent; ARDELYX, INC.; CHAO, Jianhua; JAIN, Rakesh; HU, Lily; LEWIS, Jason Gustaf; BARIBAULT, Helene; CALDWELL, Jeremy; (582 pag.)WO2018/39386; (2018); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics