Month: November 2020

42726-73-8,Some common heterocyclic compound, 42726-73-8, name is tert-Butyl methyl malonate, molecular formula is C8H14O4, 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 round bottom flask was charged with S11 (10.0 g, 0.056 mol, 1.0 equiv.), tert-butyl methylmalonate (12.3 ml, 0.074 mol, 1.3 equiv.), (S)-2-(diphenyl((trimethylsilyl)oxy)methyl)pyrrolidi-ne (3.7 g, 0.011 mol, 0.2 equiv.), and 100 mL of EtOH. The reaction mixture was stirred atroom temperature for 16 h and was then concentrated in vacuo. Purification of the crudeproduct by flash chromatography on silica gel (petroleum ether:EtOAc, 5:1 v/v) afforded S2as a pair of diastereoisomers (15.1 g, 76percent), both as yellow oil.S2-upper: TLC (petroleum ether:EtOAc, 5:1 v/v): Rf = 0.30; 1H NMR (400 MHz, CDCl3): delta 9.68 (s, 1H), 7.81 (d,J = 8.8 Hz, 1H), 7.55 (t, J = 7.2 Hz, 1H), 7.46 (d, J = 7.6 Hz, 1H), 7.39 (t, J = 8.4 Hz, 1H), 4.56 ? 4.50 (m, 1H),3.83 (d, J = 9.2 Hz, 1H), 3.57 (s, 3H), 3.12 ? 2.97 (m, 2H), 1.43 (s, 9H); 13C NMR (100 MHz, CDCl3): delta 199.6,167.9, 166.5, 150.3, 134.8, 132.8, 129.3, 128.2, 124.7, 83.2, 57.2, 52.6, 46.6, 33.7, 27.8, 27.8, 27.8; IR (neat): vmax= 1727, 1355, 845, 749 cm-1; HRMS (m/z): [M + Na] + calcd. for C17H21NNaO7, 374.1210; found 374.1210; [alpha]D25= +63.4 (c 0.20, MeOH).S2-lower: TLC (petroleum ether:EtOAc, 5:1 v/v): Rf = 0.26; 1H NMR (400 MHz, CDCl3): delta 9.68 (s, 1H), 7.82 (d,J = 8.4 Hz, 1H), 7.55 (t, J = 8 Hz, 1H), 7.46 (d, J = 7.6 Hz, 1H), 7.38 (t, J = 7.6 Hz, 1H), 4.53 ? 4.47 (m, 1H), 3.87(d, J = 9.6 Hz, 1H), 3.73 (s, 3H), 3.08 ? 2.94 (m, 2H), 1.20 (s, 9H); 13C NMR (100MHz, CDCl3): delta 199.6, 168.4,165.9, 150.2, 135.0, 132.9, 129.5, 128.2, 124.7, 82.8, 57.1, 52.7, 47.3, 34.1, 27.4, 27.4, 27.4; IR (neat): vmax =1727, 1529, 844, 787 cm-1; HRMS (m/z): [M + Na] + calcd. for C17H21NNaO7 374.1210; found 374.1210; [alpha]D25 =+32.5 (c 0.30, MeOH).

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

Reference:
Article; Wang, Xiaobei; Xia, Dongliang; Qin, Wenfang; Zhou, Ruijie; Zhou, Xiaohan; Zhou, Qilong; Liu, Wentao; Dai, Xiang; Wang, Huijing; Wang, Shuqing; Tan, Ling; Zhang, Dan; Song, Hao; Liu, Xiao-Yu; Qin, Yong; Chem; vol. 2; 6; (2017); p. 803 – 816;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

183322-16-9, 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 183322-16-9 as follows.

1.6 Synthesis of ethyl 6-nitro-3,4-bis(methoxyethoxy)benzoateThe 0.23 mol ethyl 3,4-bis(methoxyethoxy)benzoate dissolved in 230 ml of acetic acid, maintaining the temperature of the systrem at 0-5C, 60 ml concentrated nitric acid was added. warmed to room temperature for 30 min, and continue reaction for 24h. The reaction mixture was poured into the 1000 ml water, ethyl acetate extraction (5¡Á250 ml), combined with the phase, are respectively using saturated NaHCO 3 solution (3x250mL) and saturated NaCl solution (3x250mL) washing, NaSO 4 drying. Activated carbon decolourizations, revolving off a solvent to obtain oil, yield 96%

According to the analysis of related databases, Ethyl 3,4-bis(2-methoxyethoxy)benzoate, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Beijing Normal University; Qi, Chuanmin; Wang, Xiao; Li, Shilei; He, Yong; Chen, Yurong; (16 pag.)CN103193722; (2016); B;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

A common heterocyclic compound, 13671-00-6, name is Methyl 2,6-difluorobenzoate, molecular formula is C8H6F2O2, 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. 13671-00-6.

Step 3: methyl 2,6-difluoro-3-nitrobenzoateTo a solution of methyl 2,6-difluorobenzoate (68.8 g, 0.4 mol) in con. H2SO4 (300 mL) was added potassium nitroperoxous acid (48.5 g, 0.48 mol) for three times and the resulting reaction mixture was stirred at room temperature for 2 hrs. The mixture was droped into ice-water (500 mL) and filtered. The solid was washed with water and dried to afford the desired product (89 g, 100%).1H NMR (DMSC i): ? 8.49-8.43 (1H, m), 7.56-7.51 (1H, m), 3.95 (3H, s).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 2,6-difluorobenzoate, its application will become more common.

Reference:
Patent; CENTAURUS BIOPHARMA CO., LTD.; XIAO, Dengming; LI, Jijun; ZHU, Yan; HU, Yuandong; WANG, Huting; WANG, Zhe; WANG, Zanping; WEI, Yongheng; SUN, Yinghui; WU, Qiong; ZHANG, Hui; PENG, Yong; KONG, Fansheng; SUN, Ying; LUO, Hong; HAN, Yongxin; WO2013/71865; (2013); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

99548-54-6, Name is Methyl 3-bromo-2-methylbenzoate, 99548-54-6, 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.

Preparation Example 13 Under a nitrogen atmosphere, a mixture of methyl 3-bromo-2-methylbenzoate (53.00 g), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (88.10 g), bistriphenylphosphine palladium chloride (8.12 g), triphenylphosphine (6.07 g), potassium acetate (68.10 g), and dioxane (530 mL) was heated and stirred at 100 C. for 29 hours, and then cooled to room temperature. The reaction mixture was filtered through Celite and washed with ethyl acetate. The resulting filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain methyl 2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (54.00 g) as a colorless oil.

Statistics shows that Methyl 3-bromo-2-methylbenzoate is playing an increasingly important role. we look forward to future research findings about 99548-54-6.

Reference:
Patent; Negoro, Kenji; Ohnuki, Kei; Yonetoku, Yasuhiro; Kuramoto, Kazuyuki; Urano, Yasuharu; Watanabe, Hideyuki; US2012/35196; (2012); A1;,
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. 6962-92-1, name is 4-Chlorobutyl acetate, A new synthetic method of this compound is introduced below., 6962-92-1

To a suspension of sodium ethoxide (4 g, 59.18 mmol) in EtOM (50 mL) was added thiophenol (5 g, 45.45 mrnol) at0C, followed by drop-wise addition of 4-chiorobutyl acetate (7 g, 45.45 minol) over a period of 20 mm. and stirred the same temperature for 10 mm. and heated at reflux for 6 h. The RM was cooled the reaction to RT, added KOH pellets (2.6 g, 45.45 inmol), heated at reflux for4 h. After completion, the RM was poured into ice water, extracted with EtOAc (2 times), EtOAc layer was washed with water, brine, dried over anhydrous Na2SO4, filtered and the solvent was evaporated under reduced pressure to get crude compound. The crude compound was purified by silica gel(60-120 mesh) column chromatography, eluted with 8%EtOAc/pet ether to afford 4-(phenylthio)butan-1-ol as oily mass (6 g, 72%); ?H NMR (400 MHz, cdcl3) 5 7.33 (dd, J = 8.2,1.6 Hz, 2H), 7.30 – 7.23 (m, 2H), 7.20 – 7.14 (m, 1H), 3.65 (td, J = 5.0, 4.1, 3.0 Hz, 2H), 2.96 (t, J = 6.9 Hz, 2H),1.78 – 1.65 (m, 4H); Mass (M+H): 183, LCMS Purity: 99.83%.

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; SUMITOMO CHEMICAL COMPANY, LIMITED; NAKASHIMA, Yosuke; JIN, Yoshinobu; WO2014/84407; (2014); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

6933-47-7, Name is Methyl 4-amino-2-methylbenzoate, 6933-47-7, 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.

A solution of 143 3,5-dichloro-4-ethoxybenzoic acid (7: R1=Et) (285mg, 1.21mmol) and 144 DIPEA (1.05mL, 6.05mmol) in 35 DMF (2.5mL) was added to 38 HATU (690mg, 1.82mmol) and the orange mixture was stirred for 5min prior to the addition of 145 methyl 4-amino-2-methylbenzoate (8: R=R2=Me) (200mg, 1.21mmol) in DMF (1mL). The resulting dark orange solution was stirred for 18h. 2M 117 HCl (10mL) was added and stirring continued for 10min, and then the mixture was extracted with diethyl ether. The organic layer was washed with water (3¡Á15mL), dried over MgSO4, filtered and the solvent was evaporated in vacuo. The yellow residue was purified by silica gel chromatography (40g, 0-100% 45 EtOAc in 136 isohexane) to afford 146 methyl 4-(3,5-dichloro-4-ethoxybenzamido)-2-methylbenzoate (10: R1=Et, R=R2=Me) (267mg, 56%): 1H NMR (400MHz, CDCl3) delta 7.97 (d, J=8.5Hz, 1H), 7.81 (2H, s), 7.83-7.77 (1H, m), 7.59-7.48 (2H, m), 4.18 (2H, q, J=7.0Hz), 3.89 (3H, s), 2.63 (3H, s), 1.49 (3H, t, J=7.0Hz). m/z 380 (M-H)- (ES-).

Statistics shows that Methyl 4-amino-2-methylbenzoate is playing an increasingly important role. we look forward to future research findings about 6933-47-7.

Reference:
Article; Clarke, Earl; Jarvis, Christopher I.; Goncalves, Maria B.; Kalindjian, S. Barret; Adams, David R.; Brown, Jane T.; Shiers, Jason J.; Taddei, David M.A.; Ravier, Elodie; Barlow, Stephanie; Miller, Iain; Smith, Vanessa; Borthwick, Alan D.; Corcoran, Jonathan P.T.; Bioorganic and Medicinal Chemistry; vol. 26; 4; (2018); p. 798 – 814;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

619-42-1, 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.

EthynyHrimethylsilane (82.4 g. 0.84 rnol. 1.2 equiv) was added dropwise over 10 min under a nitrogen atmosphere to a soiution of methyl 4-brornobenzoate (150 g, 0.7 mol 1.0 equiv), PdC2 iPP h), (15 g, 0.021 mot.. 0.03 equiv) and Cul (13 g, 0.068 mol, 0.1 equiv) in TEA (1.5 L), The reaction was stired at 90C for 30 minutes, whereupon LCMS showed complete consumption of methyl 4-bromobenzoate. Then, the reaction mixture was filtered and the filter cake was washed with EiOAe (5 x 500 rnLj, The filtrate was concentrated under reduced pressure to give a residue, which was distilled under reduced pressure to yield methyl 4~{{triroethyi8tiyi) ethynyl) benzoate (INT-1.2) as an off-white solid (156 g, 96%).

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

Reference:
Patent; ACHAOGEN, INC.; PATTERSON, Brian, D.; LU, Qing; AGGEN, James, Bradley; DOZZO, Paola; KASAR, Ramesh, Annasaheb; LINSELL, Martin, Sheringham; KANE, Timothy, Robert; GLIEDT, Micah, James; HILDEBRANDT, Darin, James; MCENROE, Glenn, A.; COHEN, Frederick; WO2013/170030; (2013); 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. 13671-00-6, name is Methyl 2,6-difluorobenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. 13671-00-6

To 30 ml of a THF solution containing 700 mg of 2-(2-chloropyridin-3-yl)acetic acid was added dropwise 7.75 ml of a 1.9 mol/L THF solution of hexamethyldisilazane sodium at -78 C. and the mixture was stirred for 10 minutes. Then, 616 mul of methyl 2,6-difluorobenzoate was added dropwise thereto, and then, the temperature of the mixture was raised from -78 C. to room temperature and stirred for 1 hour. To the mixture was added an aqueous saturated ammonium chloride solution followed by stirring the mixture for 1 hour. Thereafter, ethyl acetate was added thereto and the liquids were separated. The obtained organic layer was washed with saturated brine, and dried over sodium sulfate. After the solvent was distilled off under reduced pressure, the obtained residue was purified by silica gel column chromatography. The title compound was obtained as 450 mg of a transparent oily product. (1215) 1H-NMR (CDCl3) delta: 8.35 (1H, dd, J=4.7, 1.8 Hz), 7.66 (1H, dd, J=7.6, 1.8 Hz), 7.44-7.43 (1H, m), 7.25 (2H, dd, J=7.6, 4.7 Hz), 7.00-6.96 (2H, m).

The synthetic route of 13671-00-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MITSUI CHEMICALS AGRO, INC.; UMETANI, Hideki; OKAYA, Shun; IKISHIMA, Hideaki; FUKUMOTO, Takeshi; NISHIDA, Akihiro; YANAGI, Masanori; NAITO, Ryohei; MASUTOMI, Koji; SHIRAKAWA, Tomomi; SAKURADA, Akane; YUTANI, Satoshi; (368 pag.)US2020/45968; (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. 1128-76-3, name is Ethyl 3-chlorobenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. 1128-76-3

General procedure: A typical procedure is as follows. Magnesium turnings (0.36 g, 15 mmol) for Grignard reagent with no pre-treatment were placed in a 100 mL four-necked flask and were heated to dry. Carbon dioxide was introduced to the flask and a balloon filled with carbon dioxide was attached to the flask. Chlorotrimethylsilane (3.17 mL, 25 mmol) in dry DMF (30 mL) was added to the flask and the reaction mixture was stirred for 30 minutes at room temperature. Ethyl benzoate 1a (0.72 mL, 5 mmol) was added dropwise by means of a syringe and the reaction mixture was stirred at room temperature until the starting material disappeared. Then the reaction mixture was carefully poured into 1 M hydrochloric acid solution (100 mL) and the product was extracted with diethyl ether (40 mL) four times. The combined organic layer was washed with 1 M potassium carbonate solution (40 mL) twice and the product was transferred to the water layer. To the combined water layers, 3 M hydrochloric acid (200 mL) was added and the product was extracted with ether (40 mL) four times. The combined ether layer was washed with water (50 mL) and brine (50 mL), dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give the product 2a.

The synthetic route of 1128-76-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Maekawa, Hirofumi; Okawara, Hikaru; Murakami, Taro; Tetrahedron Letters; vol. 58; 3; (2017); p. 206 – 209;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

110661-91-1, A common compound: 110661-91-1, name is tert-Butyl 4-bromobutanoate, 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.

Exemplification of General Procedure J:; Preparation of tert-butyl 4-(4-(3-(3-chloro-4-isopropoxyphenyl)-l,2,4-oxadiazol-5-yl)- lH-indol-l-yl)butanoate; To a solution of 3-(3-chloro-4-isopropoxyphenyl)-5-(lH-indol-4-yl)-l,2,4-oxadiazole (0.100 g, 0.283 mmol) in DMF (0.999 ml) was added NaH (0.012 g, 0.311 mmol). After about 15 min tert-butyl 4-bromobutanoate (0.095 g, 0.424 mmol) was added and the reaction mixture was heated to about 500C. After about 24h the reaction mixture was cooled to ambient temperature, concentrated in vacuo and purified by chromatography on silica gel (eluting with EtOAc/Hep) to provide tert-butyl 4-(4-(3-(3-chloro-4-isopropoxyphenyl)-l,2,4-oxadiazol-5- yl)-lH-indol-l-yl)butanoate (0.135 g, 93%) as a colorless oil that solidified on standing. LCMS (Table 1, Method c) Rt = 3.50 min, m/z 496 (M+H)+.

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, tert-Butyl 4-bromobutanoate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ABBOTT LABORATORIES; WO2008/76356; (2008); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics