Month: November 2020

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. 1193-72-2 name is 1-Bromo-2,4-dichlorobenzene, 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. 1193-72-2

Part C. tert-butyl (7bR,11aS)-6-(2,4-dichloroanilino)-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate. An oven dried three-necked round bottom flask was fitted with septa, condenser, and a stopper. The flask was charged with tert-butyl (7bR,11aS)-6-amino-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate (134 mg, 0.36 mmol), 1-bromo-2,4-dichlorobenzene (70 mg, 0.31 mmol), NaOtBu (60 mg, 0.62 mmol), and anhydrous toluene (5 mL). The solution was purged with argon at 80 C. for 25 min then cooled to room temperature. While maintaining a blanket of argon, Pd2(dba)3 (3.4 mg, 3.7 mumol), and BINAP (7 mg, 11.2 mumol) were added quickly. The resulting mixture was heated to 80 C. for 20 hours under argon while monitoring the consumption of starting material by TLC (50% ethyl acetate/hexanes). After cooling to room temperature, the dark solution was diluted with ethyl ether (10 mL) and filtered through a pad of silica, washing with ether and ethyl acetate. The resulting solution was concentrated and chromatographed (Combiflash, 95:5 to 75:25 hexanes/ethyl acetate gradient) yielding the title compound (78 mg, 48%) as a tan solid. 1H NMR (CDCl3, 300 MHz) delta 1.41 (s, 9H), 1.79-1.97 (m, 2H), 2.85-3.18 (m, 6H), 3.46-3.61 (m, 4H), 3.68 (s, 2H), 5.84 (s, 1H), 6.71 (d, 1H, J=1.9 Hz), 6.79 (d, 1H, J=1.8 Hz), 6.89 (d, 1H, J=8.8 Hz), 7.01 (dd, 1H, J=2.3, 8.8 Hz), 7.29 (d, 1H, J=2.3 Hz) ppm.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Bromo-2,4-dichlorobenzene, and friends who are interested can also refer to it.

Reference:
Patent; Robichaud, Albert J.; Fevig, John M.; Mitchell, Ian S.; Lee, Taekyu; Chen, Wenting; Cacciola, Joseph; US2004/186094; (2004); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

A common heterocyclic compound, 2770-11-8, name is 2-(4-Chlorophenoxy)aniline, molecular formula is C12H10ClNO, 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. 2770-11-8.

2-(4-Chlorophenoxy)aniline (200 mg, 0.9107 mmol, 1.1 eq) and JV-(3-acetylphenyl)-iV- ethylacetamide (169 mg, 0.827 mmol, 1 eq) were stirred in dry dichloromethane (DCM) at room temperature for 10 min. Tri-isopropoxytitanium chloride (395 muL, 1.654 mmol, 2 eq) was added to the reaction mixture which was stirred at room temperature for 16 hours. Sodium triacetoxyborohydride (700 mg, 3.308 mmol, 4 eq) was then added to the reaction mixture and was stirred at room temperature for a further 24 h. The reaction mixture was then poured onto a solution of saturated aqueous sodium bicarbonate (100 mL) and extracted with DCM (120 mL). The organic layer was washed with brine (120 mL), dried over MgSO4, filtered and concentrated to give the crude as a yellow oil. Purification of the crude by flash chromatography (ISCO) eluting with a gradient [from 25% ethyl acetate in petrol ether to 50% ethyl acetate in petrol ether] gave (87 mg, 26 %) as a white solid. 1H NMR (270 MHz, CDCl3) delta 1.05 (3H, t, J = 8.1 Hz, CH3), 1.49 (3eta, d, J = 6.4 Hz CH3), 1.67 (3H, s, CH3), 3.68 (2H, q, J= 8.1 Hz, CH2), 4.45-4.60 (2H, m, NH and CH) 6.37 (1eta, d, J = 8.2 Hz, ArH), 6.57 (IH, dt, J = 1.4, 8.2 Hz ArH), 6.75-7.06 (6H, m, ArH), 7.23-7.39 (4H, m, ArH); 13C NMR (67.5 MHz, CDCl3) delta 13.1, 22.8, 25.0, 43.8, 52.8, 112.0, 112.9, 117.2, 118.7, 119.3, 125.0, 126.1, 126.5, 128. 0, 129.8, 130.0, 138.0, 139.1, 142.8, 147.1, 156.5, 169.9 LCMS (90% MeOH and 10% H2O; Symmetry C18 reverse phase column) tr = 2.88 min; (ES+), m/z 409.2 (35ClM’, 75%), 383 (37ClM’, 25%); HRMS (ESI) calcd. for C24H25ClN2O2 (M+H)+ 409.1605, found 409.1689. 99.48% purity.

The synthetic route of 2-(4-Chlorophenoxy)aniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; STERIX LIMITED; WO2009/66072; (2009); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

The chemical industry reduces the impact on the environment during synthesis 823-57-4, name is 2-Bromo-5-chloroaniline, I believe this compound will play a more active role in future production and life. 823-57-4

Step B: Preparation of l-Bromo-4-chloro-2-iodobenzene; [0828] A suspension of 2-bromo-5-chlorobenzenamine (1 1.348 g, 54.963 mmol) in concentrated HCl (100 mL) was cooled to 0C and treated dropwise over 20 minutes (using an addition funnel) with a solution of sodium nitrite (4.5506 g, 65.955 mmol) in water (20 mL). The reaction was stirred at 00C for 75 minutes. A solution of potassium iodide (27.372 g, 164.89 mmol) in water (50 mL) was added, and the reaction was stirred at 23C. After 1 hour, the reaction was heated to 700C. After 18 hours, the reaction was diluted with EtOAc (500 mL) and washed with water (300 mL), 2N NaOH solution (300 mL), saturated sodium thiosulfate solution (300 mL) and brine (250 mL), dried over MgSO4, concentrated in vacuo, and purified by silica gel chromatography (eluant: hexane) affording 1 1.1 1 g of 1 -bromo^-chloro^-iodobenzene.

The chemical industry reduces the impact on the environment during synthesis 823-57-4. I believe this compound will play a more active role in future production and life.

Reference:
Patent; AMGEN INC.; WO2008/76427; (2008); A2;,
Chloride – Wikipedia,
Chlorides – 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. 10061-02-6, name is trans-1,3-Dichloropropene belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. 10061-02-6

A suspension of 6.66 g (0.06 mol) of (E)-1,3-dichloropropene (3), 13.82 g (0.1 mol) of potassium carbonate, and 2.53 g (0.031 mol) of ethylamine hydrochloride in 75 mL of anhydrous acetonitrile was slowly heated to the boiling point with stirring and was then refluxed until complete conversion of 3 (12-14 h, GLC monitoring). The mixture was cooled and filtered, the precipitate was washed with ethyl acetate, the organic fractions were combined and concentrated, and the product was isolated by vacuum distillation. Yield 4.24 g (73%), bp 89 C (4-5 mm). IR spectrum, nu, cm-1: 2971, 2935,2811, 1635, 1456, 1360, 1285, 1132, 934, 801. 1H NMR spectrum, delta, ppm: 1.03 t (3H, CH3, J =7.2 Hz), 2.50 q (2H, CH3CH2N, J = 7.2 Hz), 3.09 d (4H, CH2CH=, J = 6.8 Hz), 5.93 d.t (2H, CH2CH=, Jtrans = 13.2, 6.8 Hz), 6.12 d (2H, ClCH=, Jtrans = 13.2 Hz). 13C NMR spectrum, deltaC, ppm: 11.94 (CH3), 46.80 (CH3CH2N), 52.74 (2C, CH2CH=), 119.99 (2C, ClCH=), 130.41 (2C, CH2CH=). Mass spectrum, m/z (Irel, %): 193 (5) [M]+, 180 (20), 178 (32), 132 (17), 77 (33), 75 (100), 68 (49), 56 (10), 49 (9), 42 (13), 39 (29).

The synthetic route of 10061-02-6 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Shakhmaev; Sunagatullina, A. Sh.; Zorin; Russian Journal of Organic Chemistry; vol. 53; 6; (2017); p. 832 – 835; Zh. Org. Khim.; vol. 53; 6; (2017); p. 818 – 820,3;,
Chloride – Wikipedia,
Chlorides – 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. 1996-30-1, name is 3-Bromo-4-fluorochlorobenzene belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. 1996-30-1

Step 1. l-(2-Bromo-4-chlorophenyl)-lH-l,2,3-triazole. To a solution of 2-bromo-4-chloro-l- fluorobenzene (5 g, 24 mmol) and 2H-l,2,3-triazole (6.60 g, 95 mmol) in DMF (2 mL) was added K2CO3 (16.50 g, 119 mmol). The mixture was stirred at 100C for 13 h under N2 atmosphere. The mixture was diluted with water (10 mL) and extracted with EtOAc (10 mL x 2). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by column chromatography (Si02, PE: EtOAc = 100: 1 to 3: 1) to give the title compound. MS (ESI) m/z 260.0 (M+H).

The synthetic route of 1996-30-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LIU, Weiguo; EDMONDSON, Scott, D.; GUO, Zhuyan; MERTZ, Eric; OGAWA, Anthony, K.; SO, Sung-Sau; SUN, Wanying; BROCKUNIER, Linda, L.; ALI, Amjad; KUANG, Rongze; WU, Heping; WO2015/183709; (2015); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

The chemical industry reduces the impact on the environment during synthesis 56961-77-4, name is 1-Bromo-2,3-dichlorobenzene, I believe this compound will play a more active role in future production and life. 56961-77-4

Example 1 1- (2, 3-DICHLOROPHENYL)- [1, 4] diazepine (starting material) 2.25 g (10 MMOL) 1-bromo-2, 3-dichloro-benzene was dissolved in dry toluene (50 ml), 2.3 (11 MMOL) of [1, 4] diazepine-1-carboxylic acid tert-butylester was added followed by 0.2 g BINAP (2,2-bis (diphenylphosphino)-1, 1′-binaphtyl), 85 mg tris (DIBENZYLIDENEACETONE) dipalladium (0) and 1.2 g (12MMOL) SODIUM-TERT-BUTOXYDE. The reaction mixture was refluxed for eight hours and filtered. The organic layer was washed with water, dried and evaporated in vacuo. The residue was purified by chromatography and deprotected at 10 C using 20 ML ETHYLACETATE saturated with gaseous hydrochloric acid, the precipitate was filtered giving 2.1 g (yield : 75 %) hydrochloride salt of the title compound, melting at 182-3 C.

The chemical industry reduces the impact on the environment during synthesis 56961-77-4. I believe this compound will play a more active role in future production and life.

Reference:
Patent; RICHTER GEDEON VEGYESZETI GYAR RT.; WO2005/12266; (2005); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

A common heterocyclic compound, 108-41-8, name is 1-Chloro-3-methylbenzene, molecular formula is C7H7Cl, 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. 108-41-8.

General procedure: The typical procedure is as follows. Oven dried Schlenk tube was equipped with stirrer bar, was charged with aryl halides (1 mmol), acrylates (1.2 mmol), K2CO3 (2 mmol) and catalyst2 (3 mol %) in DMF medium. The reaction mixture was stirred in an oil bath at 100C under argon atmosphere for an appropriate period of time. After completion of the reaction, the reaction mixture was then cooled to room temperature and diluted with Et2O/H2O(1:1, 20 mL). The organic layer was alienated and dried with anhydrous MgSO4. The product was filtered and dried under vacuum. The resulting crude compound was purified by column chromatography on silica gel to afford the corresponding products.

The synthetic route of 1-Chloro-3-methylbenzene has been constantly updated, and we look forward to future research findings.

Reference:
Article; Nirmala, Muthukumaran; Arruri, Sathyanarayana; Vaddamanu, Moulali; Karupnaswamy, Ramesh; Mannarsamy, Maruthupandi; Adinarayana, Mannem; Ganesan, Prabusankar; Polyhedron; vol. 158; (2019); p. 125 – 134;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

29671-92-9,Some common heterocyclic compound, 29671-92-9, name is Carbamimidic chloride hydrochloride, molecular formula is CH4Cl2N2, 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: A solution of 6-chloro-3-nitropicolinonitrile (25) (0.60 g, 2.7 mmol) and an appropriate aniline was heated at 130 C in isopropanol. After 3-16 h, the solution was concentrated under reduced pressure. The precipitate obtained was neutralized with solution of ammonia in methanol to afford 26-38 as a crude product. The next step was carried out without any purification. To a suspension of 26-38 in methanol (20 mL) and concentrated hydrochloric acid (36%, 2 – 4.0 mL) was added iron powder. The mixture was refluxed until all the starting material had reacted (monitored on TLC). The hot reaction mixture was poured into water (20 mL) and stirred for 5 min. The unreacted iron was removed using a stirring bar retriever, and the aqueous solution was neutralized with ammonium hydroxide to pH 4. The solution was then extracted with chloroform (3 ¡Á 20 mL), and the combined organic layer was washed with water (2 ¡Á 5.0 mL), sodium bicarbonate solution (5.0 mL), and brine (5.0 mL) and dried over anhydrous sodium sulfate. The product (39-52) was obtained as a gummy brown semi-solid. The next step was carried out without any purification and characterization. Mixture of 39-52, chloroformamidine hydrochloride (1 g), and dimethyl sulfone (4.0 g) was heated in an oil bath at 140 C under nitrogen for 15 min. The oil bath was removed, and water (10 mL) was added slowly to the hot reaction mixture. The aqueous solution was cooled to room temperature and extracted with chloroform (3 ¡Á 5 mL) to remove dimethyl sulfone. The aqueous phase was made basic to pH 10 with ammonium hydroxide, followed by removal of water under reduced pressure. The residue was dissolved in a mixture of 50:50 methanol-acetone (v/v), and silica gel was added (3.0 g). After the removal of solvent with a rotary evaporator, the silica gel plug was loaded onto a column and eluted with 1:5 MeOH-CHCl3 (v/v). The fractions containing the required compound were evaporated under reduced pressure to afford the targeted compounds.

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

Reference:
Article; Shah, Khushbu; Queener, Sherry; Cody, Vivian; Pace, Jim; Gangjee, Aleem; Bioorganic and Medicinal Chemistry Letters; vol. 29; 15; (2019); p. 1874 – 1880;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

1996-29-8, These common heterocyclic compound, 1996-29-8, name is 1-Bromo-4-chloro-2-fluorobenzene, 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.

Reference Example-10 A solution of 1-bromo-4-chloro-2-fluoro benzene (10.0 g, 47.8 mmol) in THF was added dropwise to a suspension of magnesium (1.28 g, 52.5 mmol) in THF (50 mL) at 40 C. (oil bath temperature) in the presence of a catalytic amount of iodine in an argon gas atmosphere, whereby a Grignard reagent was prepared. The Grignard reagent was added dropwise to a solution of diethyl oxalate (8.37 g, 57.3 mmol) in THF at -50 C., and the temperature was slowly raised to room temperature, followed by stirring for 18 hours. After the reaction was completed, the reaction solution was poured into ice, then, acidified with concentrated hydrochloric acid, and the resultant product was extracted with ether (100 mL*2, 50 mL*1). The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure, whereby an orange oily crude product (12.9 g) was obtained. This was purified by silica gel column chromatography (hexane:ethyl acetate=10:1), whereby ethyl 2-(4-chloro-2-fluorophenyl)-2-oxoacetate (4.17 g, yield: 41%) was obtained as a yellow oily material. 1H-NMR (400 MHz, CDCl3): delta1.40 (t, J=7.1 Hz, 3H), 4.43 (q, J=7.1 Hz, 2H), 7.22 (dd, J=1.8 and 10.2 Hz, 1H), 7.31 (dd, J=1.8 and 8.4 Hz, 1H), 7.89 (dd, J=7.6 and 8.4 Hz, 1H). 19F-NMR (376 MHz, CDCl3): delta-109 (s, 1F).

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 1996-29-8.

Reference:
Patent; KAKEN PHARMACEUTICAL CO., LTD.; SAGAMI CHEMICAL RESEARCH INSTITUTE; KOBAYASHI, Osamu; NIIKURA, Naoko; INOUE, Tomoko; MIZUTA, Satoshi; TAKATSUNA, Reiko; HIRAI, Kenji; SHIROUZU, Kentaro; OBATA, Miyoo; (183 pag.)US2016/24110; (2016); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

1871-57-4, Adding some certain compound to certain chemical reactions, such as: 1871-57-4, name is 3-Chloro-2-chloromethyl-1-propene, 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 1871-57-4.

Step 1: methyl 14-cyclohex^l-7-meiksiotalene-7.&-dihydro-6H-indolol.2-e]fl.5]benzoxazocine-ll- carboxylate; To a solution of methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-lH-indole-6-carboxylate (prepared as described in example 9, step 1) in dry DMF (0.06 M) was added NaH (2.5 eq., 60% suspension in mineral oil). After 30 min, 3-chloro-2-(chloromethyl)prop-l-ene (1.2 eq.) was added dropwise via syringe and EPO the solution stirred at RT for 60 min. The reaction mixture was diluted with EtOAc and washed with IN aqueous HCl and with brine, dried (Na2SO4) and evaporated. The crude residue was purified by flash chromatography (10:1 PE/EtOAc), affording the pure methyl 14-cyclohexyl-7-methylene-7,8-dihydro- 6H-indolo[l,2-e][l,5]benzoxazocine-l l-carboxylate (70%) as light yellow foam; MS (ES+) m/z 402 (M+H)+.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 1871-57-4.

Reference:
Patent; ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P ANGELETTI SPA; WO2006/46030; (2006); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics