Author: Jessica.F

Application of 7664-66-6, A common heterocyclic compound, 7664-66-6, name is 4-Isopropoxyaniline, molecular formula is C9H13NO, 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 mixture of 1-(4-chlorobenzyl)-3-(ethoxycarbonylmethyl)-6-iodoquinazoline-2,4-dion (200 mg, 0.4 mmol), palladium acetate (13.5 mg, 0.06 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (52.2 mg, 0.09 mmol), cesium carbonate (261 mg, 0.8 mmol) and dioxane (4 mL) was added 4-isopropoxyaniline (0.071 mL, 0.48 mmol) under nitrogen atmosphere, and the resulting mixture was heated at reflux for 2 hours. The reaction mixture was poured into a mixture of water (100 mL) and 5% aqueous citric acid (10 mL), and the resulting mixture was extracted with ethyl acetate (100 mL). The extract was washed by water (100 mL), dried over anhydrous sodium sulphate, and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane), and the residue was precipitated by hexane to give 1-(4-chlorobenzyl)-3-(ethoxycarbonylmethyl)-6-(4-isopropoxyphenylamino)-quinazolin e-2,4-dion (7.7 mg, Yield: 3.7%) as yellow solid. 1H-NMR (delta ppm TMS/CDCl3): 1.28 (3H, t, J=7.2 Hz), 1.33 (6H, d, J=6.0 Hz), 4.24 (2H, q, J=7.2 Hz), 4.74 (1H, m), 4.88 (2H, s), 5.29 (2H, s), 5.61 (1H, s), 6.84 (2H, d, J=8.7 Hz), 6.91 (1H, d, J=9.0 Hz), 7.01 (2H, d, J=8.7 Hz), 7.11 (1H, dd, J=3.0, 9.0 Hz), 7.19 (2H, d, J=8.7 Hz), 7.30 (2H, d, J=8.7 Hz), 7.68 (1H, d, J=2.7 Hz).

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; Shionogi & Co., Ltd.; KAI, Hiroyuki; ENDOH, Takeshi; JIKIHARA, Sae; ASAHI, Kentaro; HORIGUCHI, Tohru; EP2604260; (2013); A1;,
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Electric Literature of 53087-13-1,Some common heterocyclic compound, 53087-13-1, name is 1-(Benzyloxy)-3-bromobenzene, molecular formula is C13H11BrO, 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 4 1-(3,4,5,6-Tetramethoxy-2-methylphenyl)-1-(3- benzyloxyphenyl) methanol An anhydrous tetrahydrofuran (50 ml) solution of 3,4,5,6-tetramethoxy-2-methylbenzaldehyde (14 g, 0.058 mol) was added dropwise under ice cooling to a Grignard reagent (150 ml tetrahydrofuran solution) prepared from 3-(benzyloxy)bromobenzene (18.4 g, 0.070 mol) and magnesium (1.87 g, 0.077 mol), and the resulting solution was stirred for 2 hours. The reaction solution was poured in an aqueous solution of saturated ammonium chloride and extracted with ether. The extract was washed with saturated brine and then dried. The reaction solution was filtered, the filtrate was concentrated and the obtained crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 4:1) to obtain the titled compound (23.5 g, 0.055 mol, 95%).

The synthetic route of 53087-13-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Daiichi Suntory Pharma Co., Ltd.; Daiichi Suntory Biomedical Research Limited; EP1314712; (2003); A1;,
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Synthetic Route of 707-07-3,Some common heterocyclic compound, 707-07-3, name is (Trimethoxymethyl)benzene, molecular formula is C10H14O3, 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: To a stirred solution of the respective N-carbamate-protected aminovicinal diol 4 (0.50 mmol, 1 equiv) in CH2Cl2 (10 mL, 0.05 M) were added BF3·OEt2 (50 muL, 0.050 mmol, 0.1 equiv, 1.0 M solution in CH2Cl2) and trimethyl orthobenzoate (0.13 mL, 0.75 mmol, 1.5 equiv) at r.t. The resulting mixture was refluxed or stirred at r.t. under N2 until TLC showed complete conversion of the substrate. The reaction was quenched with sat. aq NaHCO3 and extracted with EtOAc (2 ×). The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (hexane/EtOAc) to give the desired product 5.

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

Reference:
Article; Park, Heemin; Kwon, Yongseok; Shin, Jae Eui; Kim, Woo-Jung; Hwang, Soonho; Lee, Seokwoo; Kim, Sanghee; Synthesis; vol. 49; 12; (2017); p. 2761 – 2767;,
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Adding a certain compound to certain chemical reactions, such as: 207226-31-1, name is 1,3-Dibromo-5-(trifluoromethoxy)benzene, belongs to ethers-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 207226-31-1, SDS of cas: 207226-31-1

Dibromide D-l-2a (3.0 g, 9.38 mmol), sodium-tert-butoxide (1.26 mg, 13.13 mmol), BINAP (584 mg, 0.938 mmol) and tris-(dibenzylideneacetone)-palladium (85.9 mg, 0.094 mmol) are suspended in 60 mL toluene, combined with benzophenonimine (2.04 g, 11.25 mmol), and refluxed under an argon atmosphere for 3 d. Then the reaction mixture is filtered and the solvent is eliminated by distillation.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1,3-Dibromo-5-(trifluoromethoxy)benzene, and friends who are interested can also refer to it.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; WO2009/3999; (2009); A2;,
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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. 6358-77-6, name is 5-Bromo-2-methoxyaniline, A new synthetic method of this compound is introduced below., HPLC of Formula: C7H8BrNO

5-(Dimethylphosphoryl)-2-methoxyaniline (0456) To a solution of 5-bromo-2-methoxyaniline (0.404 g, 2.00 mmol) in 8 mL DMF was added dimethylphosphine oxide (0.171 g, 2.20 mmol), palladium acetate (22.4 mg, 0.0100 mmol), XANTPHOS (69.4 mg, 0.120 mmol), and potassium phosphate (0.467 g, 2.20 mmol). The mixture was purged with nitrogen, and subjected to microwaves at 150 C. for 20 minutes. The reaction mixture was concentrated and purified by silica gel chromatography (0-20% 7N ammonia in methanol:dichloromethane) to afford the desired product (0.365 g, 85% yield).

The synthetic route of 6358-77-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ARIAD PHARMACEUTICALS, INC.; Wang, Yihan; Huang, Wei-Sheng; Liu, Shuangying; Shakespeare, William C.; Thomas, Ranny M.; Qi, Jiwei; Li, Feng; Zhu, Xiaotian; Kohlmann, Anna; Dalgarno, David C.; Romero, Jan Antoinette C.; Zou, Dong; US2015/225436; (2015); A1;,
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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 36865-41-5 as follows. Quality Control of 1-Bromo-3-methoxypropane

A solution of PPh3 (42.8 g, 163.2 mmol) and 1-bromo-3-methoxypropane (25 g, 163.3 mmol) in toluene (70 mL) is heated at 150C in an autoclave for 44 h. After completion of the reaction, the mixture is filtered and the precipitate washed with toluene and dried under high vacuum for 4 h affording the title compound as a white powder: Rt (HPLC, Nucleosil C18, 10: 90-100: 0 CH3CN/H20 + 0. 1 % TFA within 5 min, then 100% CH3CN + 0. 1% TFA): 5.06 min.

According to the analysis of related databases, 36865-41-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2005/51911; (2005); A1;,
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Synthetic Route of 171290-52-1, The chemical industry reduces the impact on the environment during synthesis 171290-52-1, name is 3,5-Dimethoxyphenylacetylene, I believe this compound will play a more active role in future production and life.

The mixture 1-ethynyl-3,5-dimethoxybenzene 1e (2 g, 12.3 mmol) was dissolved in acetonitrile (15 mL), and cooled down to 0 C., then a salt of 1-chloromethyl-4-fluoro-1,4-diazonium dicyclo 2.2.2 octane bis(tetrafluoroborate) (6.6 g, 18.5 mmol) was added in portions, then stirred at room temperature overnight, the reaction solution was poured into water (50 mL), and extracted with dichloromethane (30 mL*3), and the organic phases were combined and dried over anhydrous sodium sulfate, the desiccant was removed by filtering, next the system was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=30/1), so as to obtain the title product 1-ethynyl-2-fluoro-3,5-dimethoxybenzene 17a (800 mg, yellow solid), and the yield was 36%. 1H NMR (400 MHz, CDCl3) delta 6.46 (dd, J=6.9, 2.9 Hz, 1H), 6.41 (dd, J=4.5, 3.0 Hz, 1H), 3.78 (s, 3H), 3.69 (s, 3H), 3.22 (s, 1H).

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, 3,5-Dimethoxyphenylacetylene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BEIJING INNOCARE PHARMA TECH CO., LTD.; Chen, Xiangyang; Gao, Yingxiang; Kong, Norman Xianglong; (59 pag.)US2019/210997; (2019); A1;,
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Related Products of 148583-65-7, 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. 148583-65-7, name is 4-Fluoro-2-isopropoxyaniline, This compound has unique chemical properties. The synthetic route is as follows.

(3) Synthesis of 1-(4-Fluoro-2-isopropoxyphenyl)piperazine Dihydrochloride By similar reaction and treatment to that in Example 40(3) using 4-fluoro-2-isopropoxyaniline instead of 4-fluoro-2-methoxyaniline, the title compound was obtained as purple crystals. 1H-NMR(DMSO-d6)delta: 1.31(6H, d, J=5.9 Hz), 3.25(8H, br.s), 4.67(1H, septet, J=5.9 Hz), 6.71(1H, dt, J=8.6, 2.6 Hz), 7.93(1H, dd, J=11, 2.6 Hz), 7.08(1H, dd, J=5.9, 2.6 Hz), 9.61(2H, br.s). IR(KBr): 3442, 2983, 2925, 1626, 1522 cm-1; MS(EI): 238(M+).

The chemical industry reduces the impact on the environment during synthesis 4-Fluoro-2-isopropoxyaniline. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Mitsubishi Pharma Corporation; US6455528; (2002); B1;,
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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. 22171-15-9, name is (4-(Benzyloxy)phenyl)methanamine, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 22171-15-9

2-Amino-6-chloro-nicotinic acid described in Preparation Example A-1 (220mg, 1.4mmol), triethylamine (0.47mL, 3.37mmol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (764mg, 1.73mmol) were dissolved in N,N-dimethylformamide (3mL), 4-benzyloxy-benzylamine described in Preparation Example 1 (399mg, 1.87mmol) was added thereto, followed by stirring at room temperature for 17 hours 30 minutes. After the reaction was completed, the reaction solution was poured into brine, which was then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, then concentrated, the obtained residue was purified by silica gel column chromatography (ethyl acetate : hexane = 1 : 1), and the title compound (115mg, 0.31 mmol, 22%) was obtained. 1H-NMR Spectrum (DMSO-d6) delta(ppm): 4.35 (2H, d, J=6.0Hz), 5.08 (2H, s), 6.63 (1H, d, J=8.0Hz), 6.94-6.98 (2H, m), 7.23 (2H, d, J=8.4Hz), 7.29-7.45 (5H, m), 7.52 (2H, brs), 7.97 (1 H, d, J=8.0Hz), 8.96 (1 H, t, J=6.0Hz).

According to the analysis of related databases, 22171-15-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Eisai Co., Ltd.; EP1669348; (2006); A1;,
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Electric Literature of 53087-13-1,Some common heterocyclic compound, 53087-13-1, name is 1-(Benzyloxy)-3-bromobenzene, molecular formula is C13H11BrO, 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: To a 30 mL flamed-dried flask equipped with stir bar and a nitrogen-filled balloon were added 2,2,6,6-tetramethylpiperidine (1.2 equiv) and THF (12 mL). After cooled to 0 C with an ice waterbath, n-BuLi (2.5 M in hexane, 1.2 equiv) was added dropwise and the reaction was stirred at 0 C for 0.5 h. To a 100 mL flame-dried flask equipped with a stir bar and a nitrogen-filled balloon were added THF (30 mL), benzyne precursor (1 equiv), and corresponding ketene silyl acetals9 (1.5 equiv) and was cooled to 78 C with an acetone-dry ice bath before in situ generated lithium tetramethylpiperidine was added dropwise. The reaction was monitored and aqueous NH4Cl was added upon disappearance of the benzyne precursor. After warming to rt, the reaction mixture was extracted with ethyl acetate (30 mLx3), washed with brine, and concentrated under reduced pressure. Acetonitrile (30 mL) was added to the concentrated reaction system and cooled to 0 C with an ice-water bath followed by slow addition of hydrofluoric acid (27.6 M, 10 equiv). Upon completion, the reaction was heated to 40 C overnight before water (100 mL) was added. The mixture was extracted with ethyl acetate (30 mLx3), washed with brine, and dried with Na2SO4. The combined organic extract was concentrated under reduced pressure and purified by column chromatography on silica gel to afford the following compounds. 4.6.1. 5-(Benzyloxy)-8-methylbicyclo[4.2.0]octa-1,3,5-trien-7-one (9). Compound 9 was obtained as light yellow oil (271 mg) from 6d and tert-butyl((1-methoxyprop-1-en-1-yl)oxy)dimethylsilane in 23% yield, Rf=0.6 (Hexane/EtOAc=5:1); 1H NMR (400 MHz, CDCl3) delta 7.48-7.30 (m, 6H), 7.02 (d, J7.0 Hz, 1H), 6.89 (d, J8.4 Hz, 1H), 5.45 (s, 2H), 4.21 (q, J7.2 Hz, 1H), 1.47 (d, J7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) delta 189.3 (s), 157.0 (s), 152.6 (s), 137.8 (s), 136.4 (s), 130.7 (s), 128.5 (s), 128.2 (s), 127.9 (s), 116.7 (s), 114.2 (s), 74.0 (s), 58.3 (s), 15.0 (s). IR: gamma 2964, 2927, 2360, 2342, 1756, 1602, 1571, 1473, 1452, 1386, 1273, 1161, 1125, 991, 886, 795, 767, 748, 699 cm-1. HRMS calcd for C16H14NaO2 [M+Na]+: 261.0886, found: 261.0879.

The synthetic route of 53087-13-1 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Chen; Savage, Nikolas A.; Dong, Guangbin; Tetrahedron; vol. 70; 27-28; (2014); p. 4135 – 4146;,
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