Tag: M.W=100-200

Electric Literature of 367-22-6, A common heterocyclic compound, 367-22-6, name is 4-Chloro-3-fluoroaniline, molecular formula is C6H5ClFN, 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.

Iodine chloride (20.6 ml, 1M solution in DCM, 20.6 mmol) was added dropwise to a solution of 4-chloro-3-fluoroaniline (2 g, 13.7 mmol) in methanol (35 ml) at 0C and the reaction mixture was stirred for 1 h at room temperature. Volatiles were removed under reduced pressure, water was added and the mixture was extracted with dichloromethane. The combined organic layers were washed with water, dried with Na2S04 and evaporated. The remaining residue was purified by chromatography with three consecutive columns (silica gel, heptane/EtOAc 98:2 – 93:7 and twice heptane/EtOAc 98:2 – 95:5) to obtain the title compound (2.51 g, 67%) as dark red solid. MS (ESI): 272.1 (M+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; F. HOFFMANN-LA ROCHE AG; CECCARELLI, Simona M.; CONTE, Aurelia; KUEHNE, Holger; KUHN, Bernd; NEIDHART, Werner; OBST SANDER, Ulrike; RUDOLPH, Markus; WO2013/64465; (2013); A1;,
Chloride – Wikipedia,
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These common heterocyclic compound, 2687-12-9, name is Cinnamyl chloride, 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. Application In Synthesis of Cinnamyl chloride

EXAMPLE 1 Obtaining 2-(3-N,N-diisopropylamine-1-phenylpropyl)-4-carboxyphenol (IV’a) Diisopropylamine (2.77 1, 19.65 mol) and sodium iodide (16.95 g, 0.13 mol) were loaded onto a solution of cinnamyl chloride (1 kg, 6.55 mol) in ethanol (3 1/kg) at 20/25C. The mixture was heated at internal 80-85C, the reaction conditions being maintained for 3-4 hours until the end of such reaction. The mixture was cooled at 40-45C and distilled to an internal volume of 1.3 1. The mixture was then cooled at 20-25C, water (4 1) and toluene (3 1) was added and the pH was adjusted to 1.0-1.5. The phases were decanted and dichloromethane (4 1) was loaded onto the aqueous phase, adjusting the pH again to 11.5-12.0. The phases were decanted and the organic phase was washed with water (4 1). Once the phases were decanted, the organic phase was distilled at atmospheric pressure to an internal volume of 1.3 1 in order to then load heptane (0.5 1). Again, it was distilled to 1.3 1 and heptane (2 1) was loaded. The suspension which was obtained was filtered by a prelayer, which was washed with heptane (0.5 1). The filtered organic phase was distilled at atmospheric pressure to an internal volume of 1.3 1. The amine content of the reaction mixture was determined by the potentiometric titration thereof. Acetic acid (1.2 l/kg of amine), 4-hydroxybenzoic acid (0.63 kg/kg of amine, 1 equivalent), and, then, sulfuric acid (1.1 l/kg of amine, 4.5 equivalents) were loaded onto the mixture. It was heated at internal 80-85C, the reaction conditions being maintained for 5-6 hours until the end of the reaction. The reaction mixture was cooled to 35-40C and water (10 l/kg of amine) and ethyl acetate (10 l/kg of amine) were loaded. The phases were decanted and the organic phase was washed out with water (5 l/kg). The aqueous phases were pooled; toluene (5 l/kg of amine) was loaded, the phases were decanted and n-butanol (10 l/kg of amine) was loaded onto the aqueous phase, the pH was adjusted to 7 and it was decanted. The organic phase was distilled to an internal amine volume of 1.5-2.0 l/kg and then heptane (8 l/kg of amine) was loaded. The product which crystallized was cooled at 5-10C, filtered and washed with heptane (5 l/kg of amine). The product was then dried in an oven with air circulation for 10-12 hours, obtaining a product with an overall molar yield of 40% and with a purity greater than 90%. NMR (1H) DMSO: H8: doublet 0.8-0.9 ppm 12H, H5: multiplet 2.0-2.1 ppm 2H, H6: multiplet 2.3 ppm 2H, H7: multiplet 2.8-3.0 ppm 2H, H4: triplet 4.3 ppm 1H, H1: doublet 6.8 ppm 1H, H11: multiplet 7.1 ppm 1H, H10-9: multiplet 7.1-7.3 ppm 4H, H2: doublet 7.5 ppm 1H, H3: singlet 7.8 ppm 1H. NMR(13C) DMSO: 20.52; 20.57; 30.74; 36.11; 39.72; 48.04; 114.35; 125.56; 126.43; 128.59; 128.68; 129.02; 129.47; 129.77, 145.34; 157.76; 169.90.

The synthetic route of Cinnamyl chloride has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Ragactives, S.L.U.; EP2281801; (2011); A1;,
Chloride – Wikipedia,
Chlorides – 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. 94-97-3, name is 5-Chloro-1H-benzo[d][1,2,3]triazole, A new synthetic method of this compound is introduced below., Application In Synthesis of 5-Chloro-1H-benzo[d][1,2,3]triazole

a. To a solution of 5-chloro-1H-benzotriazole (1 g) and sodium acetate (1 g) in acetic acid was added bromine (2 g). After 10 days at room temperature, the mixture was treated with a saturated solution sodium thiosulfate, neutralized with a saturated solution of sodium bicarbonate and extracted with ethyl acetate. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and the filtrate concentrated under reduced pressure to afford a residue that was purified by semi-preparative liquid chromatography to afford 4-bromo-5-chloro-1H-benzotriazole as an off-white solid (213 mg, 14%). MS (ES): M/Z [M+H]=232. 1H NMR: (400 MHz, DMSO-d6): 7.58 (d, J=8.7Hz, 2H) and 7.91 (d, J=8.7Hz, 1H).

The synthetic route of 94-97-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AVENTIS AGRICULTURE; MERIAL LIMITED; Soll, Mark David; Le Hir de Fallois, Loic Patrick; Huber, Scot Kevin; Lee, Hyoung Ik; Wilkinson, Douglas Edward; Jacobs, Robert Toms; US2014/80862; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 95-51-2, The chemical industry reduces the impact on the environment during synthesis 95-51-2, name is 2-Chloroaniline, I believe this compound will play a more active role in future production and life.

General procedure: Into a pressure microreactor of stainless steel of 17 mL capacity or into a glass ampule (20 mL) (results of the parallel runs were virtually identic) was charged 5-10 wt % of catalyst (0.94HY-BS, NaY-BS, 0.72KNaX-BS), 100 mmol of aniline or its derivative, and 400 mmol of dimethyl carbonate. The reactor was hermetically closed (the ampule was sealed), and was heated for 1-4 h at 150 C. After the end of the run the reactor was cooled to room temperature, opened, the reaction mixture was filtered through a bed of Al2O3. Dimethyl carbonate was distilled off, the residue was distilled at atmospheric pressure or in a vacuum, or crystallized from ethanol.

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, 2-Chloroaniline, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Khusnutdinov; Shchadneva; Mayakova, Yu. Yu.; Ardieva; Khazipova; Kutepov; Russian Journal of Organic Chemistry; vol. 52; 11; (2016); p. 1565 – 1570; Zh. Org. Khim.; vol. 52; 11; (2016); p. 1574 – 1578,5;,
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Chlorides – an overview | ScienceDirect Topics

Some common heterocyclic compound, 6775-78-6, name is 6-Chloroimidazo[1,2-b]pyridazine, molecular formula is C6H4ClN3, 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. Quality Control of 6-Chloroimidazo[1,2-b]pyridazine

478 mg (3.11 mmol) of 6-chloroimidazo[1 ,2-b]pyridazine were introduced into 10 mL of chloroform under argon and, while cooling in ice, 664 mg (3.73 mmol) of N-bromosuccuinimide were added. After the addition was complete, the reaction mixture was stirred at rt over night. The reaction mixture was then mixed with water and ethyl acetate and, after addition of saturated sodium bicarbonate solution, the phases were separated. The aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were then washed with sat. sodium chloride solution and dried over sodium sulfate. In the final removal of the solvent in vacuo, the desired product was isolated in quantitative yield in the form of an amorphous white solid which was employed without further chromatographic purification in subsequent reactions. 1H-NMR (CDC , stored over molecular sieves): delta [ppm] (1 H) ppm.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6775-78-6, its application will become more common.

Reference:
Patent; Bayer Intellectual Property GmbH; EIS, Knut; PUeHLER, Florian; ZORN, Ludwig; SCHOLZ, Arne; LIENAU, Philip; GNOTH, Mark, Jean; BOeMER, Ulf; GUeNTHER, Judith; HITCHCOCK, Marion; WO2013/34570; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 363-51-9, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 363-51-9, name is 2-Chloro-6-fluoroaniline, This compound has unique chemical properties. The synthetic route is as follows.

EXAMPLE 29 7-[(2-chloro-6-fluorophenyl)amino]-5-{ [2-methoxy-4-(piperazin-l- yl)phenyl]amino}pyrido[3.4-d]pyridazin-4(3H)-one EXAMPLE 29A /er/-butyl 4-(4-(7-(2-chloro-6-fluorophenylamino)-4-oxo-3,4-dihydropyrido[3,4-c/]pyridazin- 5-ylamino)-3-methoxyphenyl)piperazine-l -carboxylate A mixture of EXAMPLE 24A (370 mg, 0.76 mmol), 2-chloro-6-fluoroaniline ( 121 mg, 0.84 mmol), tris(dibenzylideneacetone)dipalladium (70 mg, 0.08 mmol), 2- dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (44 mg, 0.1 mmol), potassium tert- butoxide (257 mg, 2.28 mmol) and teri-butanol (5 mL) was heated under nitrogen at 120C for 48 hours. The mixture was concentrated and the residue was dissolved indichloromethane, washed with saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (200-300 mesh) eluting with 98/2 dichloromethane/methanol to give the title compound. MS: 596 (M + H+).

The chemical industry reduces the impact on the environment during synthesis 2-Chloro-6-fluoroaniline. I believe this compound will play a more active role in future production and life.

Reference:
Patent; ABBOTT LABORATORIES; ABBOTT LABORATORIES TRADING (SHANGHAI) COMPANY, LTD.; VASUDEVAN, Anil; PENNING, Thomas Dale; CHEN, Huanming; LIANG, Bo; WANG, Shaohui; ZHAO, Zhongqiang; CHAI, Dikun; YANG, Leifu; GAO, Yingxiang; WO2012/97682; (2012); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 2401-24-3, 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. 2401-24-3, name is 2-Chloro-5-methoxyaniline belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Example 4(i): N-(2-chloro-5-methoxyphenyl)-2-fluoroacetamideA solution of fluoroacetyl chloride (3 g, 31 ,1 mmol) was added dropwise to an ice cold solution of 2-chloro-5-methoxyaniline (5 g, 31 ,7 mmol) and triethylamine (4,5 ml, 32,3 mmol) in dichloromethane (20 ml) and left stirring overnight. Water (50 ml) was added and the biphasic mixture was stirred for 2 minutes and then separated. The aqueous phase was extracted with dichloromethane (20 ml) and the combined organic phases were dried over magnesium sulfate (5 g). After evaporation the crude solid material was used in the next step.

The synthetic route of 2-Chloro-5-methoxyaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GE HEALTHCARE LIMITED; TRIGG, William, John; JONES, Paul, Alexander; WO2015/40148; (2015); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Some common heterocyclic compound, 2613-34-5, name is 3-Chloro-2,4-difluoroaniline, molecular formula is C6H4ClF2N, 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. HPLC of Formula: C6H4ClF2N

Methyl 1 -methyl-4-[ [( 1R)-2,2,2-trifluoro- 1-methyl-ethyl] sulfamoyl]pyrrole-2-carboxylate (6.61 g, 21.03 mmol) and 3-chloro-2,4-difluoroaniline (4.13 g, 25.2 mmol) were dissolved in tetrahydrofuran (150 mL) and this was stirred and cooled in an ice-water bath. Over a period of 5minutes lithium bis(trimethylsilyl)amide in toluene (63.1 mL, 1 M, 63.1 mmol) was added dropwise. The resulting mixture was stirred for 1 h while cooling was continued. Another 2 eq of lithium bis(trimethylsilyl)amide in toluene (42.1 mL, 1 M, 42.1 mmol) were added and the resulting mixture was stirred for 1 hour at room temperature. The resulting mixture was quenched using ammonium chloride (sat. / 200 mL). The resulting mixture was extracted usingEtOAc (3 x 250 mL). The combined extracts were washed with brine (250 mL), dried on Na2SO4, filtered and concentrated in vacuo yielding a brown powder. This powder was crystallized twice out of methanol/water. The precipitation was collected on a glass filter. The obtained powder was purified by silica gel column chromatography using gradient elution from heptane to EtOAc (100:0 to 0:100). The obtained residue was crystallized again out ofmethanol/water. The white crystals were collected on a glass filter and dried in a vacuum oven at 55C for 24 hours yielding compound 120 (3.03 g) as a white powder. Differential scanning calorimetry: From 30 to 300 C at 10C/mm: peak at 217.6C.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2613-34-5, its application will become more common.

Reference:
Patent; JANSSEN R&D IRELAND; VANDYCK, Koen; HACHE, Geerwin, Yvonne, Paul; LAST, Stefaan, Julien; MC GOWAN, David, Craig; ROMBOUTS, Geert; VERSCHUEREN, Wim, Gaston; RABOISSON, Pierre, Jean-Marie, Bernard; WO2014/184350; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 53145-38-3, name is 2-Chloro-6-fluoroanisole, belongs to chlorides-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 53145-38-3, Formula: C7H6ClFO

The system 100 shown in FIG. 1 was configured with a first reactor 102 having an internal volume of about 25 ml, a transfer tube 106 having an internal volume of about 3 ml and a second reactor 104 having an internal volume of about 30 ml.Agitation was started in the first reactor 102 and the second reactor 104. The system 100 was cooled to about -60 C. by placing the first reactor 102 and the second reactor 104 in the bath 108 containing dry ice in hexane and maintained at a temperature of about -70 C. A solvent level of the bath 108 was checked to assure that the transfer tube 106 was covered with the solvent.A solution of 2-chloro-6-fluoroanisole (2,6-CFA) (31.4 g, 190 mmol) in anhydrous 1,2-dimethoxyethane (DME) (241 ml) was prepared in a 500 ml bottle. Molecular sieves were added to remove water, and water content was measured by Karl Fischer titration to assure the 2,6-CFA solution contained less than about 100 ppm water (about 35 ppm measured). The 2,6-CFA solution in the 500 ml bottle was placed on a balance and fitted with a cap holding the inlet tube to metering pump 110. (i.e, first pump 110). A mixture of n-butyllithium in hexanes (2.5 M, 102 ml) was loaded into another (syringe) pump (i.e., second pump 112) and trimethyl borate (25.7 g, 28 ml) was loaded into a syringe and was placed on a separate syringe pump (i.e., third pump 114).The first, second, and third feed lines 118, 120, 122 were respectively pumped full of the 2,6-CFA, the n-butyllithium and the methyl borate to just short of the tube exit prior to the start of the experiment. When the solvent bath temperature was about -74 C., the first pump 110 containing the 2,6-CFA and the second pump 112 containing the n-butyllithium were started with flow rates of 0.73 ml/min and 0.27 ml/min, respectively. The first feed line 118 was formed from polytetrafluoroethylene (PTFE) tubing and was directed through the reactor head port 116A into the first reactor 102 below the liquid surface. The n-butyllithium addition was added to the first reactor 102 through the second feed line 120 that terminated just above the liquid surface in the first reactor 102.The solvent bath was monitored and dry ice was added to the solvent bath to maintain the temperature of the system 100 at less than about -60 C. The third feed line 122 for the trimethyl borate was directed into the second reactor 104 to drip above the liquid surface. After about 26 minutes, when the first reactor 102 was full and the reaction mixture was flowing through the transfer tube into the second reactor 104, the third pump 114 was started at a flow rate of the trimethyl borate of about 0.08 ml/min.After about 37 minutes, as the second reactor 104 filled, flow was started from an exit tube 126 to maintain reaction mixture volume in the second reactor 104 near about 30 ml. Intermediate solution from the second reactor 104 was accumulated in the flask 124 at room temperature. The intermediate solution was weighed and transferred to sample jars every 20 to 30 minutes. The experiment was run for 4 hours. A total of about 153 g of the intermediate solution containing PBA-diMe was collected. A gas chromatography (GC) method with internal standard was used to quantify the amount of PBA-diMe in the intermediate solution. A conversion to PBA-diMe of about 92% was calculated with about 8% of the original unconverted 2,6-CFA also quantified.

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, 2-Chloro-6-fluoroanisole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; DOW AGROSCIENCES LLC; Emonds, Mark V. M.; Menning, Catherine A.; Blaylock, D. Wayne; US2013/66115; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

2106-02-7, name is 2-Chloro-4-fluoroaniline, belongs to chlorides-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. Computed Properties of C6H5ClFN

Production of ethyl (3S)-3-{[(2-chloro-4-fluorophenyl)amino]sulfanyl}-3,6-dihydro-2H-pyran-4-carboxylate To a solution (400 mL) of ethyl (3S)-3-sulfanyl-3,6-dihydro-2H-pyran-4-carboxylate (14.5 g) in dichloromethane was added dropwise tert-butyl hypochlorite (10 mL) at -78C. After stirring for 30 min, 2-chloro-4-fluoroaniline (23 mL) was added dropwise at -78C. The reaction mixture was stirred for 1 hr, and the reaction was discontinued with 5% aqueous sodium sulfite solution (300 mL). After extraction with dichloromethane (300 mL), the extract was washed with water, and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel column chromatography (hexane/ethyl acetate=15:1?5:1) to give the title compound as a crude product (20.0 g, 96.3 %ee). This product was crystallized from diisopropyl ether/hexane (120 mL, 1:5) to give the title compound (12.3 g, 62%) as white crystals. 1H-NMR (CDCl3) delta: 1.33 (3H, t, J = 7.2 Hz), 3.72-3.79 (2H, m), 4.20-4.46 (5H, m), 5.53 (1H, br s), 6.90-7.03 (3H, m), 7.54-7.59 (1H, m). enantiomeric excess: >99 %ee [column: CHIRALPAK AD (manufactured by DAICEL CHEMICAL INDUSTRIES, LTD.), mobile phase: hexane/2-propanol = 97.5/2.5].

The synthetic route of 2106-02-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Pharmaceutical Company Limited; KITAMOTO, Naomi; (26 pag.)EP2528598; (2016); B1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics