Category: 178312-47-5

These common heterocyclic compound, 178312-47-5, name is Ethyl 4,4-difluorocyclohexanecarboxylate, 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. Recommanded Product: 178312-47-5

Step 5 4,4-Difluoro-cyclohexanecarboxylic acid: A solution of 4,4-difluoro-cyclohexanecarboxylic acid ethyl ester (970 mg, 5.0 mmol) in ethanol (5 mL) was treated with 2N sodium hydroxide (3.8 mL, 7.6 mmol) at 0 C., and the mixture was allowed to warm to ambient temperature and stirred for an additional 18 hours. The mixture was diluted with water (15 mL), and the pH was adjusted to 3-4 with 6 N hydrochloric acid. The mixture was extracted with toluene, dried and concentrated to give the title compound as a white solid. Yield: 758 mg (92%). 1H-NMR (CDCl3.) delta: 1.60-2.23 (m, 8H), 2.45 (m, 1H).

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

Reference:
Patent; Auspex Pharmaceuticals, Inc.; US2008/146605; (2008); A1;,
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Electric Literature of 178312-47-5, A common heterocyclic compound, 178312-47-5, name is Ethyl 4,4-difluorocyclohexanecarboxylate, molecular formula is C9H14F2O2, 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 1; 4,4-Difluorocyclohexanecarboxamide A suspension of ethyl 4,4-difluorocyclohexanecarboxylate (2500 mg, 13 mmol) in ammonium hydroxide (28%, 50 ml) was stirred at 60 C. overnight. After removal of solvent, the residue was washed with water. The precipitate was obtained as product (white solid, 800 mg). 1H NMR (300 MHz, CDCl3): delta 5.31-5.45 (br, 2H), 2.02-2.27 (m, 3H), 1.92-2.02 (m, 2H), 1.72-1.87 (m, 4H). The mother liquor was acidified with 1N HCl to pH<1. The compound was extracted with EtOAc. The organic layer was washed with water, brine, dried over anhydrous sodium sulphate, filtered, condensed. 4,4-difluorocyclohexanecarboxylic acid was obtained as a 1200 mg of white solid which was further converted to 4,4-difluorocyclohexanecarboxamide by following procedure. The synthetic route of 178312-47-5 has been constantly updated, and we look forward to future research findings. Reference:
Patent; AstraZeneca AB; US2009/111830; (2009); A1;,
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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. 178312-47-5, name is Ethyl 4,4-difluorocyclohexanecarboxylate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. COA of Formula: C9H14F2O2

To a stirring solution of crude compound 2 (2.8 g, 14.5 mmol) in THF (50 mL) was added LiHMDS (1M in THF) (21.8 mL, 21.8 mmol) at -78 C and stirred for 1 h. To this, BOM- chloride (2.42 mL, 17.4 mmol) was added drop wise at -78 C; warmed to RT and stirred at RT for 4 h. After consumption of the starting material (by TLC), the reaction was quenched with NH4Cl solution (50 mL) and extracted with EtOAc (2 x 100 mL). The combined organic layer dried over Na2SO4 and concentrated to obtain compound 3 (2.5 g, 55%) as colorless liquid. 1H NMR (500 MHz, CDCl3) delta 7.40-7.21 (m, 5H), 4.49 (s, 2H), 4.22-4.09 (m, 2H), 3.52 (s, 1H), 3.45 (s, 1H), 2.33-2.21 (m, 2H), 2.19-1.93 (m, 2H), 1.93-1.77 (m, 2H), 1.63-1.51 (m, 2H), 1.27 (t, J = 7.1 Hz, 3H). (0435) LCMS (m/z): 313.2 [M++1]

The synthetic route of 178312-47-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; APTINYX INC.; KHAN, M, Amin; (134 pag.)WO2018/26763; (2018); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

These common heterocyclic compound, 178312-47-5, name is Ethyl 4,4-difluorocyclohexanecarboxylate, 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. Safety of Ethyl 4,4-difluorocyclohexanecarboxylate

Step 5 4,4-Difluoro-cyclohexanecarboxylic acid: A solution of 4,4-difluoro-cyclohexanecarboxylic acid ethyl ester (970 mg, 5.0 mmol) in ethanol (5 mL) was treated with 2N sodium hydroxide (3.8 mL, 7.6 mmol) at 0 C., and the mixture was allowed to warm to ambient temperature and stirred for an additional 18 hours. The mixture was diluted with water (15 mL), and the pH was adjusted to 3-4 with 6 N hydrochloric acid. The mixture was extracted with toluene, dried and concentrated to give the title compound as a white solid. Yield: 758 mg (92%). 1H-NMR (CDCl3.) delta: 1.60-2.23 (m, 8H), 2.45 (m, 1H).

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

Reference:
Patent; Auspex Pharmaceuticals, Inc.; US2008/146605; (2008); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Related Products of 178312-47-5, 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 178312-47-5 as follows.

(Reference Example 1) 4,4-Difluorocyclohexanecarboaldehyde To a solution of 173 g (0.900 mol) of 4,4-difluorocyclohexanecarboxylic acid ethyl ester in 1.0 L toluene, 945 ml (0.945 mol) of 1.0 M diisobutyl aluminum hydride-toluene solution was added dropwise at -55C or lower temperatures and then the reaction solution was stirred at -65C for 30 minutes. After completion of the reaction, saturated ammonium chloride aqueous solution was added at -40C or lower temperatures to the reaction solution and then 1.0 L of 4 N hydrochloric acid was added at 0C or lower temperatures. The organic layer was separated and then the aqueous layer was extracted with toluene, and the combined organic layers were washed with 1 N hydrochloric acid, saturated sodium hydrogencarbonate aqueous solution and saturated sodium chloride aqueous solution in order and dried with anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the obtained oily residue was subjected to distillation under reduced pressure (55-57C/6 mmHg) to provide 75.3 g of the title compound as a colorless oil (yield: 57%). 1H-NMR spectrum (300 MHz, CDCl3) delta ppm: 9.68 (1H, d, J = 1 Hz), 2.42-2.28 (1H, m), 2.16-1.70 (8H, m).

According to the analysis of related databases, 178312-47-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Daiichi Sankyo Company, Limited; UBE Industries, Ltd.; KAWAI, Yukinori; IWASE, Noriaki; KIKUCHI, Osamu; TAKATA, Katsunori; MOTOYAMA, Takahiro; HAGIHARA, Masahiko; EP2801574; (2014); 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. 178312-47-5, name is Ethyl 4,4-difluorocyclohexanecarboxylate, A new synthetic method of this compound is introduced below., HPLC of Formula: C9H14F2O2

Under nitrogen atmosphere, 2.3 g of ethyl 4,4- difluorocyclohexanecarboxylate was dissolved in 50 ml of tetrahydrofuran. Thereto 0.46 g of lithium aluminum hydride was added at 0C and the mixture was stirred at 0C for an hour. Thereafter, 1N aqueous sodium hydroxide was added to the reaction mixture, and formed solids were filtered and then washed with ethyl acetate. The filtrate and the washing solution were combined, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain (4, 4-difluorocyclohexyl) methanol.

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; WO2005/63694; (2005); 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. 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;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Synthetic Route of 178312-47-5,Some common heterocyclic compound, 178312-47-5, name is Ethyl 4,4-difluorocyclohexanecarboxylate, molecular formula is C9H14F2O2, 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 solution ofbutyllithium(2.000 mL, 2.80 mmol) was added to a cold (-78 C.) solution ofdiisopropylamine(0.396 mL, 2.80 mmol) inTHF(5 mL) under N2and the mixture was stirred at -78 C. for 1 h. A solution ofethyl 4,4-difluorocyclohexanecarboxylate(384 mg, 2 mmol) in THF (2 mL) was added at -78 C. and the mixture was stirred for 1 h and then gradually warmed to -20 C. over 2 h and then re-cooled to -78 C. Neat((chloromethoxy)methyl)benzene(0.226 mL, 2.200 mmol) was added and the mixture was allowed to warm to rt over 2 h. The reaction was quenched with satd. NH4Cl and extracted with EtOAc and washed with water, brine, dried (Na2SO4). Evaporation of the solvent afforded a lightyellowoil which was purified by silica gel FCC (1:1 DCM-hexanes) to afford1-((benzyloxy)methyl)-4,4-difluorocyclohexanecarboxylateas acolorlessoil.

The synthetic route of 178312-47-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hewawasam, Piyasena; Lopez, Omar D.; Tu, Yong; Wang, Alan Xiangdong; Xu, Ningning; Kadow, John F.; Meanwell, Nicholas A.; Gupta, Samayamuthula Venkata Satya Arun Kumar; Kumar, Indasi J. Gopi; Ponugupati, Suresh Kumar; Belema, Makonen; US2015/23913; (2015); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

178312-47-5, 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.

.4.4-Difluorocyclohexanecarbaldehvde; )-Propylmagnesium chloride (20 mL of a 2.0 M solution in THF, 40 mmol) was added dropwise to a oled (-150C) suspension of ethyl-4,4-difluorocyclohexanecarboxylate (3.0 g, 15.6 mmol) and N1O- nethylhydroxylamine hydrochloride (2.28 g, 23.4 mmol) in THF (30 mL). The reaction mixture was rred for 15 min then quenched with satd. NuH4Cl(aq). The product was extracted into ethyl acetate 2). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated to give i-difluoro-iV-methoxy-N-methylcyclohexanecarboxamide as a clear oil (3.01 g, 93% yield). ? a solution of the aforementioned Wei?reb amide (3.0 g, 14.5 mmol) in diethyl ether (30 mL) at -780C is added, dropwise, diisobutylaluminium hydride (16 mL of a 1.0 M solution in toluene).On mpletion of addition, the mixture was stirred for a further 15 min before being poured into a stirred xture of diethyl ether (50 mL), hexanes (50 mL) and IN HCl(aq) (100 mL). The mixture was stirred r 5 rnins and then the layers were separated and the organic phase dried (MgSO4) and concentrated to /e 4)4-difluorocyclohexanecarboxaldehyde.

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; MERCK SHARP & DOHME LIMITED; WO2006/134341; (2006); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

178312-47-5, name is Ethyl 4,4-difluorocyclohexanecarboxylate, 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. 178312-47-5

To a reaction mixture of 4,4-difluorocyclohexanecarboxylic acid ethyl ester (7.1 g, 37 mmol) in THF (50 mL) cooled to 0 C. was added dropwise 2.0 M lithium tetrahydroaluminate in THF (18.5 mL) over 10 min. The reaction mixture was stirred at 0 C. for 1 h. Water (5 mL) was added dropwise, followed by 1.0N NaOH (5 mL). The reaction mixture was filtered through Celite, THF was evaporated, and the resulting aqueous solution was diluted with brine (50 mL) and extracted with ethyl acetate (50 mL). The organic layer was collected, dried over anhydrous sodium sulfate, filtered, and concentrated to give the title compound as a clear oil (5.6 g) which was used without further purification.

Statistics shows that 178312-47-5 is playing an increasingly important role. we look forward to future research findings about Ethyl 4,4-difluorocyclohexanecarboxylate.

Reference:
Patent; Saito, Daisuke Roland; Long, Daniel D.; Van Dyke, Priscilla; Church, Timothy J.; Jlang, Lan; Frieman, Bryan; US2009/62333; (2009); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics