Month: March 2021

Some common heterocyclic compound, 50594-82-6, name is 3,4,5-Trichlorobenzotrifluoride, molecular formula is C7H2Cl3F3, 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: C7H2Cl3F3

Comparative Example 3: Preparation of 2,6-dichloro-4-(trifluoromethyl)phenyl- hydrazine of the formula 1-1 from 3,4,5-trichloro- benzotrifluoride in toluene; 10 g (40 mmole) of 3,4,5-trichlorobenzotrifluoride (99.7% purity) were dissolved in 30 g (326 mmole) of toluene. To this solution were added 8 g (160 mmole) of hydrazine hydrate (100%). The resulting mixture was stirred at reflux (approx. 1100C) for 24 hours. Thereafter, an organic phase of 39.4 g was separated. The solution obtained by this separation contained the product 2,6-dichloro-4-(trifluoromethyl)phenylhydrazine in an amount of 0.9 wt-% and the starting material 3,4,5-trichlorobenzotrifluoride in an amount of 26.3 wt-%, meaning that a product yield not higher than 3.6 % was obtained.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 50594-82-6, its application will become more common.

Reference:
Patent; BASF SE; WO2008/113661; (2008); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

50638-47-6, name is 4-Bromo-2-chloro-1-methoxybenzene, 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. Quality Control of 4-Bromo-2-chloro-1-methoxybenzene

To a 3-necked round bottom flask was added 4-bromo-2-chloro-1-methoxy-benzene(45.00 g, 203.18 mmol) and THF (450 mL), n-Butyllithium (2.5 M in hexanes, 90.21 mL, 1.11 eq) was added at -78 C. The mixture was stirred for 2 h at -78 C. A solution of 1,4- dioxaspiro[4.5]decan-8-one (34.91 g, 223.50 mmol) in THF (90 mL) was added dropwise to the reaction mixture. The resulting mixture was stirred for 3 h at -78 C. The reaction was quenched with aqueous NH4C1 (lOOmL) and extracted with EtOAc (500 mL). The organic layer was dried (Na2504), filtered and concentrated. The residue was washed with hexanes (350 mL), filtered and dried under high vacuum. The solid was triturated with hexanes (15 mL), filtered and dried under high vacuum to give 8-(3-chloro-4-methoxy-phenyl)-1,4- dioxaspiro[4.5]decan-8-ol (37 g, 61%) as a white solid. ?H NMR (400 IVIHz, CDC13): 7.31 (d, 1H), 7.29 (dd, 1H), 7.10 (d, 1H), 3.90-3.92 (m, 4H), 3.89 (s, 3H), 1.99-2.02 (m, 4H), 1.70- 1.73 (m, 4H); LCMS: 281.2 [M-OH].

The synthetic route of 50638-47-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; METACRINE, INC.; SMITH, Nicholas D.; GOVEK, Steven P.; NAGASAWA, Johnny Y.; (169 pag.)WO2018/170166; (2018); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 38762-41-3,Some common heterocyclic compound, 38762-41-3, name is 4-Bromo-2-chloroaniline, molecular formula is C6H5BrClN, 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.

Compound alpha (1 g, 4.8 mmol) was dissolved in 10 mL of anhydrous methylene chloride. To this mixture was added triethylamine (0.68 mL, 4.8 mmol) and the reaction was stirred at room temperature for 5 min. Acetyl chloride (0.5 mL, 7.2 mmol) was then added at 0 0C and the mixture stirred at room temperature for 2 hours. Water and dichloromethane were added and the layers separated. The organic layer was then dried over sodium sulfate and concentrated to give 1.11 g, 92% yield of compound b. To a solution of b (500 mg, 2.01 mmol), cyclopropyl boronic acid (225 mg, 2.62 mmol), potassium phosphate (1.49 g, 7.04 mmol) and tricyclohexylphosphine (56 mg, 0.2 mmol) in toluene (10 mL) and water (0.4 mL) under nitrogen atmosphere was added palladium acetate (23 mg, 0.1 mmol). T he mixture was heated to 100 0C for 3h and then cooled to room temperature. Water was added and the mixture extracted with ethyl acetate, dried over sodium sulfate and concentrated to give 550mg of crude product c that was used in the next step without further purification. Compound c (500mg, 2.4 mmol) was dissolved in 4 mL of ethanol. Aqueous IN HCl (4 mL) was added and the mixture stirred at reflux for 8 hours. The solvent was removed in vacuo to afford 440mg of compound d which was used in the next step without further purification. Compound d (440mg, 2.6 mmol) was dissolved in 14 mL of dichloromethane. Sodium bicarbonate (7 mL, sat. solution) and thiophosgene (0.2 mL, 2.6 mmol) were added and the mixture stirred at room temperature for Ih. Then, the organic layer was separated, dried over sodium sulfate and concentrated to afford 877 mg, 99% yield of compound e which was used in the next step without further purification Compound e (447mg, 2.1 mmol) was dissolved in 3 mL of dimethylformamide, aminoguanidine hydrochloride salt (355 mg, 3.2 mmol) and diisopropyl ethylamine (0.56 mL, 3.2 mmol) were added and the mixture stirred at 50 0C for 18 hours. The mixture was then concentrated and to the resulting residue was added 2M aqueous sodium hydroxide solution (10 mL). The mixture was stirred at 50 0C for 18 hours and then cooled to room temperature. The resulting mixture was then neutralized with aqueous IN HCl and the precipitate (product) collected to give compound/ (240 mg, 44% yield) Compounds/(89mg, 0.33 mmol) and g (94mg, 0.33 mmol) were dissolved in DMF (1.5 mL) and potassium carbonate (51mg, 0.37 mmol) was added. The mixture was stirred at room temperature for 18 hours. Water was then added to the mixture and the precipitate formed collected and purified by prep. TLC (90% dichloromethane/ 10% methanol) to give 116 mg, 68% yield of compound h. Dichloroacetic acid (0.04 mL, 0.46 mmol) was added to a mixture of compound h (116mg, 0.23 mmol), benzyltriethyl ammonium bromide (183mg, 0.68 mmol) and sodium nitrite (304mg, 4.6 mmol) in dibromomethane (5 mL). The mixture was stirred at room temperature for 18 hours in the dark. The reaction mixture was then concentrated and the resulting residue was purified by prep. TLC (95% dichloromethane /5% methanol) to afford 99.10 mg of the sulfonic acid and 17.90 mg of title compound i.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-Bromo-2-chloroaniline, its application will become more common.

Reference:
Patent; VALEANT RESEARCH & DEVELOPMENT; WO2006/26356; (2006); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

1435-48-9, name is 2,4-Dichloro-1-fluorobenzene, 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. HPLC of Formula: C6H3Cl2F

Add to a 2 L autoclave 194 ml (2 mol) of carbon tetrachloride and 33 g (0.2 mol) of 2,4-dichlorofluorobenzene To the reactor was added 16 g of the catalyst 8 in Table 1 above, The reaction was allowed to proceed under reflux for 30 minutes, The reactor was then cooled To room temperature, To the reaction system was added 200 ml of deionized water, Reaction at 40 C for 1 hour, After completion of the reaction, a fraction of 143-144 C (35 mmHg) was collected by distillation, To give 39.1 g of a slightly yellowish liquid, Yield 86.0%

The synthetic route of 1435-48-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Zhejiang Yongtai Technology Co ., Ltd; Li, yijun; Zhang, xing; Zhou, rixi; (12 pag.)CN104649890; (2016); B;,
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. 6276-54-6, name is 3-Chloropropan-1-amine hydrochloride, A new synthetic method of this compound is introduced below., SDS of cas: 6276-54-6

Large-Scale Synthesis of 3-Azidopropan-1-amineA solution of sodium azide (195 g, 3.0 mol) in deionized water (800 mL) was added into a three-neck round-bottom flask equipped with a condenser. Then 3-chloropropylamine hydrochloride (195 g, 1.5 mol) dissolved in 300 mL of deionized water was added. After continued stirring at 75-78 C. for 96 h, the white precipitate (NaCl) was removed as a byproduct from the reaction mixture by filtration. The yellow filtrate was basified with aqueous NaOH to pH?10-11 and further extracted with diethyl ether (5¡Á200 mL). The organic fraction was dried over anhydrous MgSO4 overnight, filtered, concentrated on a rotary evaporator, and distilled under reduced pressure to produce a colorless oil. The yield was: 108.4 g, 72%. 1H NMR (CDCl3, delta, ppm): 3.35 (t, 2H, CH2N3), 2.78 (t, 2H, NH2CH2), 1.71 (p, 2H, CH2CH2CH2), 1.27 (s, 2H, NH2).

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; Zhamu, Aruna; Jang, Bor Z.; US2013/5917; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 139512-70-2, A common heterocyclic compound, 139512-70-2, name is 4-Chloro-5-fluorobenzene-1,2-diamine, molecular formula is C6H6ClFN2, 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 12; 5-[(E)-2-(5-Chloro-6-fluoro- lH-benzimidazol-2-yl)-vinyl]-2-(4-methyl-imidazol- 1 -yl)-phenol trifluoroacetate salt; (E)-3-[3-Methoxy-4-(4-methyl-imidazol-l-yl)-phenyl]-acrylic acid (100 mg, 0.39 mmol) and 4-fluoro-5- chloro-benzene-l,2-diamine (62 mg, 0.39 mmol) were added to a 4-mL vial. Polyphosphoric acid (~1 ml) was added, the vial capped with a septum cap, and the reaction mixture heated to 2000C for 3h.The reaction was quenched with water and the precipitated solid collected. The residue was purified by preparative etaPLC Reverse phase (C- 18), eluting with Acetonitrile/Water + 0.05% TFA, to give the product (14 mg) as a brown solid.1H (600 MHz, dmso-d6): 2.32 (s, 3H), 7.18 (d, J= 16.4 Hz, IH), 7.30 (d, J= 1.8 Hz, IH), 7.35 (dd, J=1.7, 8.2 Hz, IH), 7.54 (d, J= 8.2 Hz, IH), 7.60 (d, J= 9.4 Hz, IH), 7.64-7.68 (m, 1 H), 7.74-7.76 (m,2H), 9.33 (s, IH).LCMS (ESI): calcd for C19H14ClFN4O [M+H]+ 369.1, found 369.1

The synthetic route of 139512-70-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK & CO., INC.; WO2008/97538; (2008); A1;,
Chloride – Wikipedia,
Chlorides – 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 1939-99-7 as follows. Safety of Phenylmethanesulfonyl chloride

To a solution of 2-((tert-butyldimethylsilyl)oxy)ethanamine (11.7 g, 66.6 mmol) and triethylamine (11.2 mL, 79.9 mmol) in tetrahydrofuran (222 mL) at 0 C was slowly added phenylmethanesulfonyl chloride (12.7 g, 66.6 mmol) portion wise and the reaction was stirred at room temperature for 16 hours. MTBE was then added and the Et3N?HCl salt was removed byfiltration. The filtrate was then concentrated and purified by silica gel solumn chromatography (0-30% Acetone in heptane, 216 nM) to N-(2-((tert-butyldimethylsilyl)oxy)ethyl)-1- phenylmethanesulfonamide (17.8 g, 81 % yield). LCMS (ESI), mlz, 330. [M+H]+.

According to the analysis of related databases, 1939-99-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; FAUBER, Benjamin; RENE, Olivier; (86 pag.)WO2017/102796; (2017); 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. 60811-21-4, name is 4-Bromo-2-chloro-1-fluorobenzene, A new synthetic method of this compound is introduced below., Quality Control of 4-Bromo-2-chloro-1-fluorobenzene

A dry, argon-flushed Schienk-flask equipped with a magnetic stirrer and a septum was charged with 20 mL freshly titrated iPrMgClLiCI (1.24 M in THE, 1.0 equiv.) to which 3.8 mL of diisopropylamine (1.1 equiv.) was added dropwise at 25 00. The reaction mixture was stirred at this temperature until gasevolution was completed (ca. 48 h). The formed precipitate was dissolved with additional dry THE. The fresh solution of iPr2NMgCILiCI in THE was titrated at 25 00 with benzoic acid and 4- (phenylazo)diphenylamine as an indicator. A concentration of 0.59 M was obtained.To a solution of 4-bromo-2-chloro-1 -fluoro-benzene (0.209 g, 1 .00 mmol) in THE (1 mL) was added iPr2NMgCILiCI (0.59 M, 3.39 ml, 2.00 mmol) at 25 00 and the resulting mixture was stirred for 15 mm at25 c Hexachloro-2-propanone (0.397 g, 1 .50 mmol) was added at 0 00 and the mixture was stirred for15 mm. The resulting mixture was then quenched with sat. aq. NH4CI, extracted with ethyl acetate and dried over anhydrous Na2SO4. After filtration, the solvent was removed in vacuo. Quantitative GO measurement showed that the ratio between 5-bromo-1 ,3-dichloro-2-fluoro-benzene and regioisomer is about 12:1. Purification by flash column chromatography (Si02, i-hexane) furnished 5-bromo-1 ,3-dichloro-2-fluoro-benzene (0.190 g) as a colorless oil.

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; SYNGENTA PARTICIPATIONS AG; SMITS, Helmars; KNOCHEL, Paul; KLATT, Thomas; BECKER, Matthias; (18 pag.)WO2016/58895; (2016); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

These common heterocyclic compound, 2401-24-3, name is 2-Chloro-5-methoxyaniline, 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. name: 2-Chloro-5-methoxyaniline

3-bromo-6-methoxy-2-methylpyridine (Aldrich catalog No.758191-1G,0.3 g, 1.485 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (0.053 g, 0.111 mmol), cesium carbonate (0.581 g, 1.782 mmol) and palladium (II) acetate (0.017 g, 0.074 mmol) were added to a microwave vial. Then, 2-chloro-5-methoxyaniline (Chemimpex catalog No.27675, 0.246 g, 1.559 mmol) was added. The solvent was degassed with argon twice. The reaction was heated on a heating block to 100 C. for 15 hours. The crude reaction mixture was cooled to room temperature and then filtered through celite. The celite was rinsed repeatedly with ethyl acetate to collect the crude product mixture. A reverse-phase column was run (water, acetonitrile) to give N-(2-chloro-5-methoxyphenyl)-6-methoxy-2-methylpyridin-3-amine (0.286 g, 69% yield). 1H NMR (CDCl3, 400 MHz) delta 7.42 (d, 1H, J=8.4 Hz), 7.20 (d, 1H, J=8.4 Hz), 6.60 (d, 1H, J=8.4 Hz), 6.26 (dd, 1H, J=2.8, 8.8 Hz), 6.00 (d, 1H, J=2.8 Hz), 5.65 (s, 1H), 3.93 (s, 3H), 3.66 (s, 3H), 2.37 (s, 3H).

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

Reference:
Patent; OssiFi Inc.; Ellies, Debra; Rey, Jean-Philippe; Kimball, F. Scott; US2014/288068; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 103724-99-8, A common heterocyclic compound, 103724-99-8, name is 2-Bromo-5-chloro-1,3-dimethylbenzene, molecular formula is C8H8BrCl, 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 400 mL vessel equipped with a mechanical stirrer, thermometer, distillation head and dropping funnel, solid sodium hydroxide (10.9 g, 0.27 mol, microprills with 0.5 – 1 mm diameter) is charged under an inert atmosphere.1-Methyl-2-pyrrolidone (NMP, 137 g) is added to the vessel in one portion through the dropping funnel and the reaction mixture cooled to 10 – 15 C while stirring. A solution of malononitrile (NEC-CH2-CEN) (6.6 g, 0.10 mol) in NMP (8.9 g) is added through the dropping funnel over 10 – 15 minutes maintaining the temperature at 10 – 15 C. The reaction mixture is then heated to 100 C and a vacuum (30 mbar) applied, upon which solvent (40 g) is distilled off.2-Bromo-5-chloro-1 ,3-dimethyl-benzene (20 g, 0.089 mol) is then added through the dropping funnel over 5- 10 minutes, whilst maintaining the temperature at 100- 110 CC. A mixture containingpalladium (II) chloride (0.19 g, solution in conc. hydrochloric acid, assay 20% Pd, 0.36 mmol), triphenylphosphine (0.45 g, 1.6 mmol) and NMP (18 g) is then added through the dropping funnel over a 5 – 10 minute period. The temperature is allowed to rise to 124 C and the reaction mixture stirred at this temperature for 2 – 3 hours. Conversion is monitored by pulling samples and subsequent HPLC analysis.When conversion is complete, a vacuum (20-40 mbar) is applied and solvent (90 g) is distilled off. The resulting residue is cooled below 100 C and water (95 g) is added. After cooling to room temperature, the resulting mixture is filtered through hyflo (Hyflo SuperCel diatomaceous earth, ca. 10 g) and the filter cake washed with water (20 g). To the combined filtrates, hydrochloric acid (20.6 g, assay 32%, 0.18 mol) is added to adjust the pH from 13.3 to 2.7.The resulting mixture is extracted with tert-butyl-methyl ether (2 x 110 g). The organic phases are washed with water (2 x 50g) and the combined organic phases evaporated to dryness. The resulting solid residue is recrystallized from iso-propanol (63 g) and the resulting crystals filtered, washed with cold iso-propanol (5 g) and dried under vacuum to yield 2-(4-chloro-2,6-dimethyl-phenyl)propanedinitrile (melting point (m.p.) 145 – 147 C).

The synthetic route of 103724-99-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SYNGENTA PARTICIPATIONS AG; ZELLER, Martin; FEDOU, Nicolas; (19 pag.)WO2018/15489; (2018); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics