Month: March 2021

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. 178312-47-5, name is Ethyl 4,4-difluorocyclohexanecarboxylate, A new synthetic method of this compound is introduced below., Application In Synthesis of Ethyl 4,4-difluorocyclohexanecarboxylate

A solution of butyllithium (1.600 mL, 4.00 mmol) was added to cold (- 78 C) solution of diisopropylamine (0.565 mL, 4.00 mmol) in THF (5 mL) under nitrogen and the mixture was stirred at -78 C 1 h. A solution of ethyl 4,4- difluorocyclohexanecarboxylate (384 mg, 2 mmol) in THF (2 mL) was added at – 78 C and the mixture was stirred for 1 h. The mixture was gradually warmed to – 20 C over 2 h and then recooled to – 78 C and connected to a balloon of oxygen and stirred at – 78 C for 1 h. The reaction mixture was added satd. NaHSC solution (5 mL) and allowed to warm to rt and stirred at rt overnight. The reaction mixture was diluted with ether and organic layer separated, washed with water, brine, dried ( a2S04). Evaporation of the solvent afforded a light yellow oil which was purified by silica gel FCC (DCM) to afford ethyl 4,4-difluoro- 1 -hydroxy – cyclohexanecarboxylate as a colorless oil (143 mg). NMR (400MHz,CHLOROFORM-d) delta 4.28 (q, J= 7.3 Hz, 2 H), 2.23 (br. s, 1 H), 2.19 – 1.99 (m, 6 H), 1.83 – 1.73 (m, 2 H), 1.33 (t, J= 1.0 Hz, 3 H).1 N NaOH (0.382 mL, 0.382 mmol) was added to a solution of ethyl 4,4- difluoro-l -hydroxy cyclohexanecarboxylate (26.5 mg, 0.127 mmol) in THF (0.5 mL) and methanol (0.5 mL) and the mixture was stirred at rt overnight. The reaction mixture was acidified with 2 N HC1 and extracted with EtOAc, washed with brine and dried (MgS04). Evaporation of the solvent afforded Cap-9 as a white solid.XH NMR (400MHz, CHLOROFORM-d) delta 2.21 – 2.01 (m, 5 H), 1.92 – 1.87 (m, J= 6.8, 3.2, 3.2 Hz, 2 H), 1.86 – 1.79 (m, J= 6.7, 3.1 Hz, 2 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; BRISTOL-MYERS SQUIBB COMPANY; HEWAWASAM, Piyasena; LOPEZ, Omar D.; TU, Yong; WANG, Alan Xiangdong; XU, Ningning; KADOW, John F.; MEANWELL, Nicholas A.; GUPTA, Samayamunthula Venkata Satya Arun Kumar; KUMAR, Indasi J. Gopi; PUNUGUPATI, Suresh Kumar; BELEMA, Makonen; WO2015/5901; (2015); A1;,
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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. 70347-04-5, name is Methyl 4-methoxy-3-methylbenzoate, A new synthetic method of this compound is introduced below., Product Details of 70347-04-5

Reference example 57 Methyl 3-bromomethyl-4-methoxybenzoate To a solution of methyl 3-methyl-4-methoxybenzoate (3.0g, 16.5mmol) which was prepared in Reference example 56 in carbon tertachloride (100ml) were added N-bromosuccinimide (2.9g, 16.5mmol) and benzoyl peroxide (0.10g), and the mixture was refluxed for 6 hours. After being cooled to 0C, the precipitate was filtered, and to the filtrate was added a saturated aqueous sodium thiosulfate solution (1ml). The solution was stirred for 15 minutes and concentrated in vacuo. To the residue was added water and the solution was extracted with chloroform 50 ml*3). The organic layer was concentrated and the precipitated solid was filtered to give the titled compound as a white solid (3.0 g, 11.7 mmol). Yield: 70%. 1H NMR(CDCl3)delta 8.04-7.99(2H, m), 6.91(1H, d, J = 8.6 Hz), 4.55(2H, s), 3.97(3H, s), 3.89(3H, s).

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; Dainippon Sumitomo Pharma Co., Ltd.; AstraZeneca AB; EP1728792; (2006); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Synthetic Route of 41841-16-1, 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. 41841-16-1 name is Methyl 2-(4-bromophenyl)acetate, 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.

Preparation of Intermediate methyl 1-(4-bromoDhenyl)cvclobutanecarboxylate (1AH-1); Sodium hydride (3.5g, 88mmol) was stirred as a suspension in dimethylformamide (250ml) under argon. This was warmed to 35C and methyl 2-(4-bromophenyl)acetate (10g, 44mmol) in dimethylformamide (10OmL) was added drop wise over 1 hour and then stirred at 300C for 1 hour. To this the 1 ,3-dibromopropane (4.4ml, 44mmol) in dimtheylformamide (50ml) was added drop wise over 1 hour, and this was left to stir at room temperature overnight. The reaction was incomplete. Sodium hydride (3.5g, 88mmol) was prepared in dimethylformamide (100ml) at 35C and was added to this drop wise to the reaction mixture over 1 hour. This was again left to stir at room temperature overnight. Saturated aqueous ammonium chloride solution (200ml) was carefully added, followed by water (500ml). The product was extracted with ethyl acetate (2 x 500ml), washed with water (3 x 500ml), and brine (2 x 500ml). The organic solution was then dried over magnesium sulfate, filtered, and evaporated. The crude product was purified by flash chromatography (12.5% ethyl acetate in heptane)to methyl 1-(4-bromophenyl)cyclobutanecarboxylate (900mg, 3.3mmol, 7.5%).1 H NMR (400MHz CDCI3) 7.45 (d, 2H), 7.15 (d, 2H), 3.65 (s, 3H), 2.80 (m, 2H), 2.45 (m, 2H), 2.05 (m 1 H), 1.85 (m, 1 H)

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

Reference:
Patent; PFIZER INC.; ASPNES, Gary, Erik; DOW, Robert, Lee; MUNCHHOF, Michael, John; WO2010/86820; (2010); 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 56741-34-5 as follows. name: Methyl 5-amino-2-fluorobenzoate

EXAMPLE 8 Methyl 2-bromo-3-(3-methoxycarbonyl-4-fluorophenyl)propionate To a solution of methyl 5-amino-2-fluorobenzoate (4.12 g) in 47% hydrobromic acid (11.4 ml), methanol (20 ml) and acetone (50 ml), a solution of sodium nitrite (1.88 g) in water (3 ml) was slowly added dropwise under cooling with salt-ice and stirring so as to keep an internal temperature of not higher than -5 C. After stirred for 30 minutes as it was, ice bath was removed, methyl acrylate (13.3 ml) was added, and cuprous oxide (225 mg) was added little by little while stirring vigorously. After no nitrogen became to generate, the reaction liquor was concentrated under reduced pressure. The residue was dissolved into ethyl acetate, washed with water, saturated aqueous solution of sodium hydrogencarbonate and water in order, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by means of silica gel column chromatography (developing solvent; n-hexane:ethyl acetate=10:1) to obtain 3.48 g (45%) of aimed compound as an oily material. 1 H NMR (CDCl3), delta: 3.25 (1H, dd, J=7.3, 14.6 Hz), 3.46 (1H, dd, J=7.8, 14.2 Hz), 3.75 (3H, s), 3.93 (3H, s), 4.38 (1H, t, J=7.8 Hz), 7.09 (1H, dd, J=8.8, 10.8 Hz), 7.38 (1H, ddd, J=2.4, 4.4, 8.8 Hz), 7.80 (1H, dd, J=2.4, 6.3 Hz) MS(m/z): 318, 320 (M+)

According to the analysis of related databases, 56741-34-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Kyorin Pharameuticals Co., Ltd.; US6001862; (1999); A;,
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. 39503-51-0, name is Methyl 5-bromo-2,4-dimethoxybenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. name: Methyl 5-bromo-2,4-dimethoxybenzoate

To potassium isopropylidene trifluoroborate (4.87 g, 32.7 mmol) and 5-bromo-2,4-dimethoxybenzoic acid methyl ester (7.5 g, 27.3 mmol) in THF (195 ml) was added Cs2CO3 (26.6 g, 81.8 mmol) in water (39 ml). The reaction was degassed and Pd(PPh3)4 (1.58 g, 1.36 mmol) added. The reaction was heated at reflux for three days then quenched by adding water and extracted with EtOAc (¡Á2). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated to leave an orange solid. The product was taken up in EtOAc again and the precipitate filtered. The filtrate was evaporated to dryness to yield 5-isopropenyl-2,4-dimethoxy-benzoic acid methyl ester (6.2 g). 1H NMR (Me-d3-OD) 7.68 (1H, s), 6.66 (1H, s), 5.10-5.08 (1H, m), 5.02-5.00 (1H, m), 3.93 (3H, s), 3.92 (3H, s), 3.84 (3H, s), 2.08-2.06 (3H, m). MS: [M+H]+ 237.

The synthetic route of 39503-51-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; US2010/152184; (2010); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Electric Literature of 5326-50-1, A common heterocyclic compound, 5326-50-1, name is Ethyl 2-(1-hydroxycyclohexyl)acetate, molecular formula is C10H18O3, 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.

[0338] To a solution of X4 (510 mg) in MeOH was added IN aqueous NaOH. The reaction mixture was stirred at 6O0C for Ih, and then concentrated in vacuo. The residue was diluted with water, washed with Et2O and the aqueous layer acidified with IN aqueous citric acid and extracted with EtOAc. The organics were dried (MgSO4) and concentrated in vacuo to yield after recrystallization compound X5 (220mg): 1H-NMR (CDCl3, 500MHz) 3.63 (s, 1 H), 2.45 (s, 2H), 1.22- 1.64 (m, 1 OH) ppm; FIA m/z 157.2 ES”.

The synthetic route of 5326-50-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2008/106139; (2008); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Application of 99548-54-6, 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. 99548-54-6 name is Methyl 3-bromo-2-methylbenzoate, 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.

A mixture of compound 32-1 (7 g, 40 mmol), methyl 3-bromo-2-methylbenzoate (11 g, 48 mmol), K3P04 (25 g, 120 mmol), Pd2(dba)3 (915 mg, 1 mmol), X-phos (952 mg, 2 mmol) in 100 mL of dried toluene was heated under a N2 atmosphere at 100C for 18 h. Then water (200 mL) wasadded,and the mixture was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na2SO4 and concentrated to give the crude product. The crude product was purified by flash column chromatography on silica gel eluted with petroleum ether:ethyl acetate (3:1) to give 32-2. MS (ESI) m / e (M+H): 323.1.

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

Reference:
Patent; MERCK SHARP & DOHME CORP.; HAGMANN, William K.; NARGUND, Ravi P.; BLIZZARD, Timothy A.; JOSIEN, Hubert; BIJU, Purakkattle; PLUMMER, Christopher W.; DANG, Qun; LI, Bing; LIN, Linus S.; CUI, Mingxiang; HU, Bin; HAO, Jinlai; CHEN, Zhengxia; WO2014/19186; (2014); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Application of 251458-15-8, These common heterocyclic compound, 251458-15-8, name is Methyl 2-(3-bromophenyl)-2-methylpropanoate, 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.

INTERMEDIATE 82-(3 -Bromophenyl)-2-methylpropionic acidSodium hydroxide (2M, 20 mL) was added to a solution of Intermediate 7 (6.5 g) in MeOH (20 mL) and THF (20 mL). The resulting mixture was refluxed for 2 h. The mixture was evaporated, and the residue partitioned between water and DCM (100 mL each). The aqueous phase was acidified (2M hydrochloric acid) and extracted with DCM (100 mL then 50 mL). The combined organic phases were dried (MgSO4) and the solvent removed in vacuo to give the title compound (4.55 g, 68% over two steps) as a cream solid. deltaH (CDCl3) 7.54 (s, IH), 7.40 (d, IH), 7.33 (d, IH), 7.21 (t, IH), 1.59 (s, 6H).

The synthetic route of 251458-15-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; UCB PHARMA S.A.; BUeRLI, Roland; HAUGHAN, Alan, Findlay; MACK, Stephen, Robert; PERRY, Benjamin, Garfield; RAPHY, Gilles; SAVILLE-STONES, Elizabeth, Anne; WO2010/52448; (2010); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Electric Literature of 13195-64-7,Some common heterocyclic compound, 13195-64-7, name is Diisopropyl malonate, molecular formula is C9H16O4, 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.

General procedure: 2-(2-nitrovinyl)-phenol or 2-(2-nitrovinyl)-naphthol 1, base, Cat., and 1.5 mL solvent were added to an oven-dried tube, successively. Then malonate ester or related compound 2 and oxidant were added. The reaction mixture was then stirred in air until the reaction was nearly completed, as determined by TLC. Once 1 consumed, the reaction mixture was cooled to ambient temperature. The resulting mixture was concentrated in vacuo and directly purified by column chromatography (petroleum ether/ethyl acetate = 7:1-5:1) on silica gel to give the desired products 3.

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

Reference:
Article; Leng, Jiaying; Meng, Jiang; Luo, Xiaoyan; Deng, Wei-Ping; Tetrahedron; vol. 74; 49; (2018); p. 6993 – 6999;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 88709-17-5, These common heterocyclic compound, 88709-17-5, name is Ethyl 2-ethoxy-4-methylbenzoate, 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 chilled solution of diisopropylamine (67.5 ml, 0.48 mol)in THF (500 ml) a solution of n-Butyllithium in hexane (1.2 M, 300ml) was added, maintaining the temperature between -20 to -25C and stirred for l hour at ‘-15 to -25 C. After chilling the reactionmixture to about -75 C, a solution of ethyl 2-ethoxy-4-methylbenzoate (50 g, 0.24 mol) in THF (100 ml) was added,maintaining the temperature between -70 to -75 C and stirred for2.5 hours. A solution of ssoc-anhydride (57.6 g, 0.26 mol) in THF(50 ml) was added, maintaining the temperature between -70 to -75 C and stirred for l hour. After warming the reaction mixture toabout -10 C, water (500 ml) was added and stirred. The organiclayer was preserved and aqueous layer was further extracted withethyl acetate (2 x 500 ml). The extracts were combined withoriginal organic layer and combined organic phase was washedwith water and brinoe. The product was isolated by evaporating theiorganic layer underreduced pressure. Yield: 50 g, 67.5% To a chilled solution of diisopropylamine (13.5 L, 96 mol) inTHF (100 L) a solution of n-Butyllithium in hexane (1.2 M, 60 L)was added, maintaining the temperature between -20 to -25 Cand stirred for 2 hour at -15 to -25 C. After chilling the reactionmixture to about -75 C, l,3-dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidinone (30 L)was added followed by a solution of ethyl 2-ethoxy-4-methylbenzoate (10 Kg, 48 mol) in THF (20 L),maintaining the temperature between -70 to -75 C and stirred for3 hours. A solution of Boc-anhydride (11.5 Kg, 52 mol) in THF (10L) was added, maintaining the temperature between -70 to -75 Cand stirred for 1.5 hour. After warming the reaction mixture toabout -10 C, water (100 L) was added and stirred. The organiclayer was preserved and aqueous layer was further extracted withethyl acetate (2 x 100 L). The extracts were combined with originalorganic layer and combined organic phase was washed with waterand brine. The product was isolated by evaporating the organiclayer under reduced pressure. Yield: 12.0 Kg, 81 %To a chilled solution of diisopropylamine (67.5 ml, 0.48 mol)in THF (500 ml) a solution of n-Butyllithium in hexane (1.2 M, 300ml) was added, maintaining the temperature between -20 to -25C and stirred for l hour at -15 to -25 C. After chilling the reactiormixture to about -75 C, hexamethylphosphoramide (100 ml) wasadded followed by a solution oef ethyl 2-ethoxy-4-methylbenzoate(50 g, 0.24 mol) in THF (100 ml), maintaining the temperaturebetween -70 to -75 C and stirred for 2.5 hours. A solution of Boc-anhydride (57.6 g, 0.26 mol) in THF (50 ml) was added,maintaining the temperature between -70 to -75 C and stirred forl hour. After warming the reaction mixture to about -10 C, water(500 ml) was added and stirred. The organic layer was preservedand aqueous layer jwas further extracted with ethyl acetate (2 x500 ml). The extracts were combined with original organic layerand combined organic phase was washed with water and brine.The product was isolated by evaporating the organic layer underreduced pressure. Yield: 55 g, 74%.

The synthetic route of 88709-17-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BIOCON LIMITED; WO2005/19140; (2005); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics