Month: May 2021

Synthetic Route of 870563-60-3, 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. 870563-60-3, name is (4-Fluoro-2-methoxyphenyl)methanamine belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a stirred solution of ethyl 2-(l-bromo-2-ethoxy-2-oxoethyl)benzoate (Othman, M.; Decroix, B: Synth. Comm. 1996, 26, 2803) (945 mg, 3 mmol) in acetonitrile (15 mL) containing triethyl amine (835muL, 6 mmol) a solution of 4-fluoro-2-methoxybenzylamine (698 mg, 4.5 mmol) in acetonitrile (1 mL) was added dropwise under argon at O0C. The reaction, mixture was stirred at ambient temperature for 2 h. The mixture was diluted with ethyl acetate (50 mL), washed with water and brine. The organic phase was dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography on silica gel using heptane/ethyl acetate (3:2) as an eluent to yield ethyl 2- (4-fluoro-2-methoxybenzyl)-3-oxoisoindoline-l-carboxylate as yellowish oil (857 mg, o/o).IH NMR (400 MHz, CDCl3) delta ppm 7.84 – 7.88 (m, 1 H), 7.67 – 7.76 (m, 1 H), 7.59 – 7.65 (m, 1 H), 7.46 – 7.58 (m, 2 H), 7.28 – 7.33 (m, 1 H)5 6.58 – 6.66 (m, 1 H), 5.21 (d, 1 H), 4.96 (s, 1 H), 4.47 (d, 1 H), 4.17 – 4.38 (m, 2 H), 3.82 (s, 3 H), 1.32 (q, 3 H) MS (ESI) m/z 344 [M+H], MS (ESI) m/z 342 [M-H]

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, (4-Fluoro-2-methoxyphenyl)methanamine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ASTRAZENECA AB; WO2008/8020; (2008); 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 88149-49-9 as follows. Formula: C7H4Br2F3NO

a) N-(2,6-dibromo-4-(trifluoromethoxy)phenyl)acetamide To a solution of 2,6-dibromo-4-(trifluoromethoxy)aniline (5.0 g, 14.9 mmol) in acetic acid (10 mL) was added acetic anhydride (2.1 mL, 22.5 mmol) and the mixture stirred for 48 hrs at 90° C. The resulting residue was cooled to room temperature, poured into ice water and the resulting precipitate collected by filtration, washed with water and dried under vacuum to yield N-(2,6-dibromo-4-(trifluoromethoxy)phenyl)acetamide.

According to the analysis of related databases, 88149-49-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Janssen Pharmaceutica NV; Sui, Zhihua; Subasinghe, Nalin; US2014/275172; (2014); A1;,
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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. 349-60-0, name is 1-Methoxy-3,5-bis(trifluoromethyl)benzene belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 1-Methoxy-3,5-bis(trifluoromethyl)benzene

In each of the examples in Table 3A, the substrate is reacted with the base in THF to form a metallic organoborate intermediate under the temperature and time conditions specified in Table 3A. The metallic organoborate intermediate is then reacted with the electrophile, E, in THF to form the functionalized products 11b to 11g under the following conditions:Furthermore, disubsituted anisole derivative such as lOf lead after metalation using 2b (25 °C, 0.5 h) followed by cross-coupling (ZnCl2 (10 molpercent), Pd(OAc)2 (3 molpercent), S-Phos (6 molpercent), 65 °C, 1 h) with 12 (0.8 equiv) to the functionalized anisole llf in 96percent yield (Table 3A, entry 6). In particular, tmpBEtyMgCl LiCl (2.2 mL, 1.0 M in THF, 2.2 mmol) was added dropwise at 25 °C to a solution of 3- bis(trifluoromethyl)anisole (lOf; 488 mg, 2.0 mmol) in THF (2 mL) in a flame-dried and Argon-flushed Schlenk-tube equipped with septum and magnetic stirring bar. After stirring for 30 min at 25 °C, ZnCl2 (0.2 mL, 1 M in THF, 10 molpercent), Pd(OAc)2 (14 mg, 3 molpercent), S-Phos (25 mg, 6 molpercent) and ethyl 4-iodobenzoate (12; 441 mg, 1.6 mmol) were added followed by continuously stirring for 1 h at 65 °C. After cooling to 25 °C, the reaction mixture was diluted with Et^O (5 mL) and quenched with sat. NH4C1 (aq.) (5 mL). The aqueous layer was extracted with CH2CI2 (3x 15 mL). The combined organic phases were dried over Na2SC>4 and the solvent was removed under vacuum. Flash column chromatography (pentane-Et^O, 95:5) afforded llf (602 mg, 96percent) as a white solid

The synthetic route of 349-60-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; HAAG, Benjamin; WO2012/85169; (2012); A1;,
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Synthetic Route of 4457-67-4, 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 4457-67-4 as follows.

Step 1. (S)-3,4-Dihydro-6-chloro-4-hydroxy-2-(4-methoxybutyl)-2H-thieno[3,2-e]-1,2-thiazine-1,1-dioxide (6, R3 =CH2 CH2 CH2 CH2 OCH3) A mixture of (S)-3,4-dihydro-6-chloro-4-hydroxy-2H-thieno[3,2-e]-1,2-thiazine-1,1-dioxide (5, 65.4 g) and potassium carbonate (113.3 g) in dimethylsulfoxide (350 mL) was treated with 1-bromo-4-methoxybutane (20.6 g) and the mixture was stirred at ambient temperature for 4 hours. Another 20.6 grams of 1-bromo-4-methoxybutane was then added and the mixture was stirred at ambient temperature for 18 hours. TLC analysis after this period indicated incomplete reaction, so another 4.6 grams of 1-bromo-4methoxybutane was added and the mixture was stirred at ambient temperature for another 3 hours. At this point, TLC indicated complete reaction. The mixture was poured into saturated aqueous sodium chloride (1 L) and extracted with diethyl ether (3*150 mL). The organic phase was washed sequentially with 100 mL each of 10percent aqueous sodium hydroxide, 1:1 5.25percent sodium hypochlorite/water, and saturated aqueous sodium chloride, dried over sodium sulfate, and stripped of solvent by rotary evaporation. Residual solvent was removed under vacuum to provide 82 grams (92percent) of (S)-3,4-dihydro-6-chloro-4-hydroxy-2-(4-methoxybutyl)-2H-thieno[3,2-e]-1,2-thiazine-1,1-dioxide as a light yellow oil: IR (film) 3500, 3350, 3070, 2950, 2850, 1525, 1480, 1440, 1380, 1330, 1160, 1120, 1080, 1020, 1100 cm-1; [alpha]25D +11.4° (c=1.1, methanol); Anal. Calcd for C11 H16 ClNO4 S2: C, 40.55; H, 4.95; N, 4.30. Found: C, 40.47; H, 4.99; N, 4.27.

According to the analysis of related databases, 4457-67-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Alcon Laboratories, Inc.; US5344929; (1994); A;,
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Application of 4132-48-3,Some common heterocyclic compound, 4132-48-3, name is 4-Isopropylanisole, molecular formula is C10H14O, 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.

A CH2CI2 (350 mL) solution of 1-isopropyl-4-methoxy benzene (25 g, 166 mmol) and 3-chloro-propionyl chloride (21 mL, 216 mmol), at room temperature, was treated with AIC13 (33 g, 249 mmol) in 1-2 g portions over a 1 h period. Stirring was maintained at room temperature for 24 h, then the mixture was poured onto crushed ice, and then conc. HCI (30 mL) was added. The mixture was diluted with CH2CI2 (300 mL), washed with 2 N NaOH, dried (magnesium sulfate), and concentrated in vacuo a pale yellow oil. Flash chromatography (10% EtOAc/Heptanes) yields 6-isopropyl-2, 3- dihydro-4H-chromen-4-one (7.5 g, 24%). Rf = 0.3. HRMS (ESI+) calc’d for C12Hl4O2 mlz 191. 1072 [M+H] + ; found 191.1071.

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

Reference:
Patent; ELAN PHARMACEUTICALS, INC.; WO2005/87714; (2005); A2;,
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121588-79-2, name is trans-4-Methoxycyclohexanamine, belongs to ethers-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: C7H15NO

Example 625: (2R)-2-[6-(5-chloro-2-{[trans-4-methoxycyclohexyl]amino}pyrimidin-4-yl)-1 – oxo-2,3-dihydro-1 H-isoindol-2-y l]-N-[(1 S)-2-hydroxy-1 -(3- methoxyphenyl)ethyl]propanamide (3479) (3480) A mixture of (R)-2-(6-(2,5-dichloropyrimidin-4-yl)-1-oxoisoindolin-2-yl)-N-((S)-2-hydroxy-1-(3- methoxyphenyl)ethyl)propanamide (Preparation 352, 0.1 g, 0.199 mmol), DIPEA (0.070 ml, 0.399 mmol) and trans 4-methoxycyclohexanamine (0.039 g, 0.299 mmol) (0.024 ml, 0.232 mmol) in 1 :1 EtOH:dioxane (1 mL) was heated at 80C under nitrogen overnight. The mixture was allowed to cool to room temperature and was concentrated under vacuum. The residue was dissolved in EtOAc and transferred into a separating funnel. 1 N HCI was added and the crude product was extracted with EtOAc. The combined organic extracts were washed with NaHC03, brine, dried (MgS04) and absorbed on silica. The crude product was purified by chromatography on the Companion (12 g column, 0- 5 % MeOH in DCM) to afford the title compound (0.06g, 050.1 %) as a white solid after trituration and evaporation from Et.20. 1 H NMR (DMSO-d6) delta: 8.56 (d, 1 H), 8.44 (s (br), 1 H), 8.07 – 8.01 (m, 1 H), 7.97 (d, 1 H), 7.75 (d, 1 H), 7.52 (s (br), 1 H), 7.28 – 7.19 (m, 1 H), 6.93 – 6.85 (m, 2H), 6.83 – 6.76 (m, 1 H), 5.06 – 4.96 (m, 1 H), 4.89 (t, 1 H), 4.85 – 4.80 (m, 1 H), 4.77 (d, 1 H), 4.60 (d, 1 H), 3.75 (s, 3H), 3.73 – 3.63 (m, 1 H), 3.57 – 3.52 (m, 2H), 3.23 (s, 3H), 3.16 – 3.06 (m, 1 H), 2.05 – 1.91 (m, 4H), 1.45 (d, 3H), 1.39 – 1.13 (m, 4H). LCMS: [M+H]+ = 594.

The synthetic route of 121588-79-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; OTSUKA PHARMACEUTICAL CO., LTD.; BERDINI, Valerio; BUCK, Ildiko Maria; DAY, James Edward Harvey; GRIFFITHS-JONES, Charlotte Mary; HEIGHTMAN, Thomas Daniel; HOWARD, Steven; MURRAY, Christopher William; NORTON, David; O’REILLY, Marc; WOOLFORD, Alison Jo-Anne; COOKE, Michael Liam; COUSIN, David; ONIONS, Stuart Thomas; SHANNON, Jonathan Martin; WATTS, John Paul; (867 pag.)WO2017/68412; (2017); A1;,
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Application of 888318-22-7, 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. 888318-22-7, name is 1-Bromo-3,4-difluoro-2-methoxybenzene belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Step 2: Synthesis of 1-bromo-3,4-difluoro-2-methoxy-5-nitrobenzene Under a N2 gas blanket at room temperature, a solution of Tf2O (1 M in DCM, 7.5 mL) was added dropwise to a stirred suspension of tetramethylammonium nitrate (1.02 g, 7.5 mmol) in 7.5 mL of DCM. After stirring 1.5 h at room temperature, the stirred suspension was cooled to -78 C. To the stirred nitronium triflate suspension was added dropwise 3 dissolved in 2 mL of DCM. The cooling bath was then removed and allowed to warm to room temperature. The reaction mixture was quenched with saturated solution of NaHCO3. The solution was extracted with DCM (2×20 mL). The organic layers were combined, separated, dried over Na2SO4, and concentrated under vacuum. The residue was purified through column chromatography (eluent: hexanes/EtOAc=32/1) to afford YH10 as oil (720 mg, 54%). 1H NMR (300 MHz, CDCl3): 8.12 (ddd, J=5.0, 4.0, 2.5 Hz, 1H), 4.19 (d, J=1.2 Hz, 3H).

The synthetic route of 1-Bromo-3,4-difluoro-2-methoxybenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; THE REGENTS OF THE UNIVERSITY OF MICHIGAN; Wang, Shaomeng; Zhao, Yujun; Zhou, Bing; Aguilar, Angelo; Liu, Liu; Bai, Longchuan; McEachern, Donna; Sun, Duxin; Wen, Bo; Luo, Ruijuan; Zhao, Ting; Chinnaiyan, Arul; Asangani, Irfan A.; Stuckey, Jeanne; Meagher, Jennifer Lynn; Ran, Xu; US2015/246923; (2015); A1;,
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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. 2186-92-7, name is P-anisaldehyde dimethyl acetal, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 2186-92-7

Phenyl 4,6-O-anisylidene-2,3-di-O-p-methoxybenzyl-1-thio-beta-D-glucopyranoside (3). To the solutionof 2 (20.0 g, 73.5 mmol) in the mixed solvent (CH3CN-DMF 735 mL:200 mL) were addedp-anisaldehyde dimethyl acetal (25.0 mL, 147 mmol) and (±)-camphor-10-sulfonic acid (CSA)(680 mg, 2.94 mmol) at 0 C. After stirring for 2.5 h at room temperature as the reaction wasmonitored by TLC (10:1 CHCl3-MeOH), the reaction was quenched by the addition of triethylamine.The reaction mixture was concentrated and diluted with EtOAc, of which solution was then added toseparatory funnel. After addition of distilled water to the solution, the desired 4,6-O-anisylidenatedproduct was appeared as a pure crystalline material (26.0 g, 91%), the physical data of which wasidentical to those reported in the literature [31]. To a solution of the 4,6-O-anisylidenated productobtained (2.00 g, 5.13 mmol) in DMF (25.7 mL) was added sodium hydride (492 mg, 20.5 mmol) at 0 C.After stirring for 1 h at 0 C, p-methoxybenzyl chloride (2.8 mL, 20.5 mmol) was added to themixture. After stirring for 17 h at rt as the reaction was monitored by TLC (1:2.5 EtOAc-n-hexane),the reaction was quenched by MeOH at 0 C. Dilution of the mixture with EtOAc provided a solution,which was then washed with H2O, satd aq NaHCO3 and brine. The organic layer was subsequentlydried over Na2SO4 and concentrated. The resulting residue was purified by silica gel columnchromatography (1:3 EtOAc-n-hexane) to give 3 (2.94 g, 91%). [alpha]D +3.3 (c 0.3, CHCl3); 1H-NMR(500 MHz, CDCl3) delta 7.54-6.82 (m, 17H, 4Ar), 5.54 (s, 1H, ArCH), 4.85 (d, 1H, Jgem = 10.9 Hz,ArCH2), 4.78-4.70 (m, 4H, ArCH2, H-1), 4.35 (dd, 1H, J5,6 = 5.2 Hz, Jgem = 10.3 Hz, H-6), 3.81-3.76(m, 11H, 3OCH3, H-3, H-6′), 3.66 (t, 1H, J3,4 = J4,5 = 9.5 Hz, H-4), 3.45 (m, 2H, H-2, H-5); 13C-NMR(125 MHz, CDCl3) delta 160.0, 159.4, 159.3, 133.1, 132.2, 130.5, 130.2, 129.9, 129.8, 129.0, 127.8,127.3, 113.8, 113.6, 101.1, 88.3, 82.7, 81.4, 80.1, 75.5, 74.9, 70.2, 68.6, 55.3, 55.2. HRMS (ESI) m/z:found [M+Na]+ 653.2180, C36H38O8S calcd for [M+Na]+ 653.2180.

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 2186-92-7.

Reference:
Article; Konishi, Miku; Imamura, Akihiro; Fujikawa, Kohki; Ando, Hiromune; Ishida, Hideharu; Kiso, Makoto; Molecules; vol. 18; 12; (2013); p. 15153 – 15181;,
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These common heterocyclic compound, 4132-48-3, name is 4-Isopropylanisole, 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. Quality Control of 4-Isopropylanisole

Example 55; N-((1S, 2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(4S)-6- isopropyl-3,4-dihydro-2H-chromen-4-yl] amino} propyl) acetamide; Step One; 6-isopropyl-2,3-dihydro-4H-chromen-4-one; A CH2C12 (350 ml) solution of 1-isopropyl-4-methoxy benzene (25 g, 166 mmol) and 3-chloro-propionly chloride (21 ml, 216 mmol), at r. t. , was treated with AlCl3 (33 g, 249 mmol) in 1-2 g portions over a 1 h period. Stirring was maintain at r. t. for 24 h at which time the mixture was poured onto crushed ice followed by the addition of 30 ml of conc. HC1. The mixture was diluted with 300 ml of CH2Cl2 and carefully washed (avoid emulsion) with 2 N NaOH. The organic layer was dried over MgSO4 and concentrated in vacuo a pale yellow oil. Flash chromatography (10% EtOAc/Heptanes) yields 6-isopropyl- 2,3-dihydro-4H-chromen-4-one (7.5 g, 24%).

The synthetic route of 4-Isopropylanisole has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ELAN PHARMACEUTICALS, INC.; PHARMACIA & UP JOHN COMPANY; WO2005/95326; (2005); A2;,
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Application of 1236000-51-3, 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. 1236000-51-3, name is N-Methyl-1-(4-(trifluoromethoxy)phenyl)methanamine hydrochloride belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Intermediate 41 3-butyn-1-yl(methyl)({4-[(trifluoromethyl)oxy]phenyl}methyl)amine (N-methyI-N-({-4-[(trifluoromethyl)oxy]phenyl}methyl)-3-butyn-1-amine). To a solution of Intermediate 1 (0.480 g) in dry acetonitrile (6 ml) under N2 atmosphere were added K2CO3 (0.792 g) and Intermediate 40 (0.324 g) consecutively. The mixture was refluxed for 4 days, then concentrated to dryness under vacuum. EtOAc and H2O were added, the organic layer washed with H2O (2x) and brine (1x), then dried over Na2SO4. Elimination of the solvent under vacuum gave an oil which was purified by column chromatography on silica gel, eluting with a mixture 3% EtOAc/CH2CI2 to afford 0.18O g of the title compound as a colourless liquid.1H NMR (delta, ppm, CDCI3): 7.36 (d, 2H); 7.16 (d, 2H); 3.54 (s, 2H); 2.64 (t, 2H); 2.41 (td, 2H); 2.25 (s, 3H); 1.98 (t, 1 H). [ES MS] m/z 258 (MH+).

The synthetic route of N-Methyl-1-(4-(trifluoromethoxy)phenyl)methanamine hydrochloride has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXO GROUP LIMITED; BUENO-CALDERON, Jose Maria; FERNANDEZ-MOLINA, Jorge; LEON-DIAZ, Maria Luisa; MALLO-RUBIO, Araceli; MANZANO-CHINCHON, M Pilar; WO2010/81904; (2010); A1;,
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