Category: 685-88-1

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. 685-88-1, name is Diethyl fluoromalonate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Quality Control of Diethyl fluoromalonate

2-fluoromalonic acid diethylester is manufactured from 2-chloromalonic acid diethylester and l,8-diazabicyclo[5,4,0]undec-7-ene- l,37HF neat at 80C, as described in example 2 of US 7,145,046. The raw product is hydrolyzed, in analogy to example 1 of DE-Offenlegungsschrift 4120704, by contacting it with NaOH in water (concentration of NaOH : 30% by weight). Resulting ethanol is removed by distillation, and the resulting solution is contacted withLewatit S 100 in the H-form (i.e. comprising acidic H+). The aqueous solution of fluoromalonic acid is mixed with toluene, and at a reduced pressure(400 mbar), a water/toluene mixture is removed.The resulting fluoromalonic acid then reacted with acetone as described by D. Davidson and S. A. Bernhard in J. Chem. Soc. 70(1948), page 3428, 1. paragraph in chapter “Experimental”. The fluoromalonic acid is suspended in acetic anhydride and concentrated sulfuric acid is added. The amounts of the reagents and starting compounds correspond to those described by Davidson et al.The acetone is added under cooling. After a post-reaction phaseof 2 hours, 5-fluoro-2,2-dimethyl-l,3-dioxane-4,6-dione can be isolated.

The synthetic route of 685-88-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SOLVAY SA; BRAUN, Max Josef; WO2013/79397; (2013); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 685-88-1, name is Diethyl fluoromalonate, belongs to esters-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 685-88-1, Computed Properties of C7H11FO4

Example 4 4,6-Dihydroxy-5-fluoropyrimidine 30% sodium methoxide in methanol (63.0 g, 0.35 mol) are rapidly admixed with formamide (33.75 g, 0.75 mol) and the mixture is heated to reflux temperature. At reflux, ethyl fluoromalonate (17.8 g, 95.0 mmol, content: about 95%) is then added over a period of 200 min, and the mixture is stirred at reflux temperature for a further 3 h. The suspension is concentrated completely under reduced pressure, the residue is dissolved in water (65 ml) and the pH of the solution is adjusted to pH 1 using 30% HCl. The resulting precipitate is then filtered off with suction and dried at 100 C. under reduced pressure overnight. This gives 4,6-dihydroxy-5-fluoropyrimidine (12.1 g, content (HPLC-STD): 90.2%; 88.3% of theory) as a solid.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Diethyl fluoromalonate, and friends who are interested can also refer to it.

Reference:
Patent; Bayer Aktiengesellschaft; US6255486; (2001); B1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 685-88-1,Some common heterocyclic compound, 685-88-1, name is Diethyl fluoromalonate, molecular formula is C7H11FO4, 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: Synthesis of 2-( 1 -(2,3 -difluorobenzyl)-5 -(difluoromethoxy)- 1 H-pyrazol-3 -yl)-5- fluoropyrimidine-4,6-diol To a mixture containing diethyl 2-fluoromalonate (2 equiv.) and1 -(2,3 -difluorobenzyl)-5 -(difluoromethoxy)- 1 H-pyrazole-3 -carboximidamide hydrochloride (Described in step 3 towards the synthesis of Compound 1-52 (1 equiv.) in methanol was added a 25 wt% solution of sodium methoxide in methanol (5 equiv.). The mixture was stirred at 23 C for 1 h. To this mixture, was added HC1 (5 equiv.). The mixture was stirred vigorously for 15 mm. The precipitate formed was collected by filtration and dried under vacuum to deliver the desired intermediate, 2-( 1 -(2,3 -difluorobenzyl)-5-(difluoromethoxy)- 1 H-pyrazol-3 -yl)-5 -fluoropyrimidine-4,6-diol (475 mg, 44 % yield) as a cream colored solid.?H NMR (500 MHz, DMSO-d6) ppm 7.19 – 7.57 (m, 3 H), 7.11 – 7.16 (m, 1 H), 6.71 (s, 1 H), 5.41 (s, 2H).

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

Reference:
Patent; IRONWOOD PHARMACEUTICALS, INC.; RENHOWE, Paul Allen; SHEPPECK, James Edward; NAKAI, Takashi; IYER, Karthik; PERL, Nicholas Robert; RENNIE, Glen Robert; WO2015/89182; (2015); 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. 685-88-1, name is Diethyl fluoromalonate, A new synthetic method of this compound is introduced below., SDS of cas: 685-88-1

General procedure: All flasks and stirrer bars were flame dried before use. Tothe N-oxide (0.2 mmol, 1.0 equiv.), dissolved in 2 cm3dichloromethane was added Tf2O (0.3 mmol, 1.5 equiv.) at0 C. In another flask, a suspension of NaH (0.7 mmol, 3.5equiv.) in 1 cm3 tetrahydrofuran was cooled to 0 C andthe malonate (0.7 mmol, 3.5 equiv.) was added. After15 min, the malonate solution was added to the activatedN-oxide solution and the mixture was stirred at roomtemperature for 1 h. The reaction was quenched withNH4Cl solution and the aqueous phase was extracted withdichloromethane. The combined organic layers werewashed with brine before being dried over MgSO4. Thesolvents were removed under reduced pressure and thecrude product was purified by column chromatography.

The synthetic route of 685-88-1 has been constantly updated, and we look forward to future research findings.

Reference:
Erratum; Lemmerer, Miran; Teskey, Christopher J.; Kaiser, Daniel; Maulide, Nuno; Monatshefte fur Chemie; vol. 149; 4; (2018); p. 721 – 722;,
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. 685-88-1, name is Diethyl fluoromalonate, A new synthetic method of this compound is introduced below., Safety of Diethyl fluoromalonate

Part A: A mixture of sodium metal (1.55 g, 67.4 mmol) and EtOH (15.0 mL, 257 mmol) was stirred at RT until nearly all sodium had reacted. Diethyl fluoromalonate (3.54 mL, 22.4 mmol) was added followed by acetamidine hydrochloride (2.14 g, 22.7 mmol). The reaction mixture was heated at reflux for 3 h, cooled to RT and concentrated under reduced pressure. The residue was diluted with water (ca. 50 mL) and acidified (pH=2) with 6M aqueous HCl, and the mixture was stirred at RT for 1 h as a precipitate formed. The solids were collected by suction filtration and washed with water. Excess solvent was removed in vacuo to give 4,6-dihydroxy-5-fluoro-2-methylpyrimidine (2.08 g, 64%) as a light gray solid. LCMS (m/z): 145 (M+H)+

The synthetic route of 685-88-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ICAGEN, INC.; US2007/197523; (2007); 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. 685-88-1, name is Diethyl fluoromalonate, A new synthetic method of this compound is introduced below., Recommanded Product: Diethyl fluoromalonate

General procedure: All flasks and stirrer bars were flame dried before use. To the N-oxide (0.2 mmol, 1.0 equiv.), dissolved in 2 cm3 dichloromethane was added Tf2O (0.3 mmol, 1.5 equiv.) at 0 C. In another flask, a suspension of NaH (0.7 mmol, 3.5equiv.) in 1 cm3 tetrahydrofuran was cooled to 0 C and the malonate (0.7 mmol, 3.5 equiv.) was added. After 15 min, the malonate solution was added to the activated N-oxide solution and the mixture was stirred at room temperature for 1 h. The reaction was quenched with NH4Cl solution and the aqueous phase was extracted with dichloromethane. The combined organic layers were washed with brine before being dried over MgSO4. The solvents were removed under reduced pressure and the crude product was purified by column chromatography.

The synthetic route of 685-88-1 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Lemmerer, Miran; Teskey, Christopher J.; Kaiser, Daniel; Maulide, Nuno; Monatshefte fur Chemie; vol. 149; 4; (2018); p. 715 – 719;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Related Products of 685-88-1, These common heterocyclic compound, 685-88-1, name is Diethyl fluoromalonate, 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 diethyl 2 fluoromalonate ester (1.0 g, 5.617 mmol) was added ethanol (10 ml), water (10ml), and lithium hydroxide monohydrate (0.943 g, 22.47mmol), then the reaction was stirred well for 16h at 50C. Then the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted in MTBE and water, then mixture was acidify with 6N HCl and then extracted with MTBE (5 x 50 ml). The combined organic layer were dried over Na2SO4, filtered and concentrated under reduced pressure to give 400 mg (yield 58%) of a white solid corresponding to 2-fluoromalonic acid. The crude product used in the next step without further purification. Synthesis of 2,4-dichloro-3-fluoroquinoline, intermediate 348-I-2

The synthetic route of 685-88-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GENOSCIENCE PHARMA; BRUN, Sonia; BERET, Antoine; BASSISSI, Firas; HALFON, Philippe; COURCAMBECK, Jerome; (275 pag.)WO2017/191599; (2017); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Synthetic Route of 685-88-1, These common heterocyclic compound, 685-88-1, name is Diethyl fluoromalonate, 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.

b) Fluoro[(phenylmethoxy)methyl]propanedioic acid, diethyl ester In a 500 ml. flask, sodium hydride (4.08 g., 102 mmole, 60% dispersion in mineral oil) was suspended in dry tetrahydrofuran (100 ml.). The suspension was cooled to -20C., and benzyl chloromethyl ether (18.6 ml., 134 mmole) was added via syringe. To the resulting mixture was added a solution of diethyl fluoromalonate (12 g., 67.4 mmole) in dry tetrahydrofuran (300 ml.) via addition funnel (rinsed with 5 ml. of solvent). The mixture was warmed to 0C. and stirred for 3 hours. Then, the mixture was warmed to room temperature and stirred for 1.5 hours. The mixture was cooled to 0C. and quenched with dry ethanol (20 ml.). The reaction solution was stirred at room temperature for 30 minutes, and then slowly poured into saturated ammonium chloride (300 ml.) at 0C. The mixture was diluted with diethyl ether (300 ml.) and separated. The aqueous layer was further extracted with diethyl ether (2 x 100 ml.), and the combined organic layers were washed with saturated aqueous sodium bicarbonate (2 x 100 ml.). The organic layer was dried over sodium sulfate, filtered, and the solvent was removed by rotary evaporation to afford 31 g. of a brown oil. Flash chromatography (16 – 20% ethyl acetate-hexane) afforded 18.8 g. of the title compound.

The synthetic route of 685-88-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; E.R. SQUIBB & SONS, INC.; EP554025; (1993); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 685-88-1, name is Diethyl fluoromalonate, belongs to esters-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 685-88-1, COA of Formula: C7H11FO4

Diethyl 2-fluoromalonate (5 g, 28.1 mmol) was added, over 10 min, to a stirred suspension of sodium hydride (1.347 g, 33.7 mmol) in tetrahydrofuran (50 mL) at 0C and the resulting colourless solution was stirred at 0 C for 15 min. and then at RT for 30 min. The solution was cooled to 0 C, a solution of 6-bromohex-l-ene (4.58 g, 28.1 mmol) in THF (20 mL) was then added over 5 min. and the resulting reaction mixture was heated to 60 C and stirred for 16 h. Then the reaction mixture was cooled to 0 C, quenched with ice cold water (100 mL) and extracted with ethyl acetate (2 x 200 mL). The combined organic layer was washed with water (200 mL), brine (200 mL), dried over anhydrous sodium sulphate, filtered and the filtrate concentrated under reduced pressure. The crude product was purified by combiflash chromatography (80 g Redisep S1O2 column, eluting with 10 % EtOAc in n- hexanes) to afford the title compound 162A (5 g, 68%) as a colourless oil. LC-MS retention time = 3.30 min; m/z = 261.2 [M+H]+ KINETIX XB-C18, (75 X 3) mm, 2.6 micron column; Flow rate: 1 mL/min; Mobile Phase A: 10 mM HCO2NH4 in 98% Water/ 2% ACN; Mobile Phase B: 10 mM HCO2NH4 in 2% Water/ 98% ACN; 20% B to 100% B over 4.6 min, then hold 0.4 min. at 20% B with flow rate 1.5 mL/min; Detection: UV at 220 nm. NMR (400MHz, CDCh) delta ppm 5.78 (ddt, J=17.1 , 10.3, 6.6 Hz, 1H), 5.01 (d, J=17.2 Hz, 1H), 4.95 (d, J=6.4 Hz, 1H), 4.34 (q, J=5.6 Hz, 4H), 2.18 – 2.05 (m, 4H), 1.43 – 1.40 (m, 4H), 1.30 (t, J=7.2 Hz, 6H).

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 fluoromalonate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; DEVASTHALE, Pratik; MOORE, Fang; ZHAO, Guohua; PIENIAZEK, Susan Nicole; SELVAKUMAR, Kumaravel; DHANUSU, Suresh; PANDA, Manoranjan; MARCIN, Lawrence R.; (384 pag.)WO2018/89355; (2018); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics