Month: May 2021

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. 15799-79-8, name is 3-Methoxy-N,N-dimethylaniline, A new synthetic method of this compound is introduced below., category: ethers-buliding-blocks

[0095] (S)-4-Benzoyloxy-3-(4-dimethylamino-2-methoxy-phenyl)-butyraldehyde (Table 1, entry 4): To a 2-dram vial equipped with a magnetic stir bar was added (2S,5S)-5-benzyl-2-tertbutyl-3-methylimidazolidin-4-one (24.6 mg, 0.100 mmol, 0.100 equiv), N,N-dimethyl-anisidine hydrochloride (18.8 mg, 0.100 mmol., 0.100 equiv), CHCl3 (1.00 ml), and N,N-dimethyl-m-anisidine (132 uL, 0.900 mmol, 0.900 equiv). The solution was cooled to -20o C. before 4-benzoyloxy-crotonaldehyde (0.380, 2.00 mmol, 2.00 equiv) was added as a solid. After 24 h, the reaction mixture was subjected directly to silica gel chromatography. Gradient elution with 10-25% EtOAc in hexanes followed by concentration and removal of residual pentenal under vacuum afforded the product as a colorless oil in 89% yield (304 mg, 0.889 mmol); 92% ee. IR (film) 2940, 2892, 2836, 2724, 1719, 1615, 1518, 1273, 1240, 1117, 712.5 cm-1; 1H NMR (300 MHz, CDCl3) ?9.74 (t, J=2.1 Hz, 1H, CHO), 8.01 (ddd, J=0.6, 1.1, 6.3 Hz., 2H, ArH), 7.58-7.40 (m, 3H, ArH), 7.08 (d, J=8.2 Hz, 1H, ArH), 6.30 (dd, J=2.5, 8.5 Hz, 1H, ArH), 6.25 (d, J=2.4 Hz, 1H, ArH), 4.51 (dd, J=5.5, 10.7 Hz, 1H, CH2O), 4.42 (dd, J=8.2, 10.7 Hz, 1H, CH2O), 4.08-3.98 (m, 1H, ArCH), 3.83 (s, 3H, OCH3), 2.98-2.80 (m, 2H, CH2CO), 2.95 (s, 6H, N(CH3); 13C NMR (75 MHz, CDCl3) 202.2, 166.6, 158.2, 151.3, 133.1, 130.3, 129.8, 129.0, 128.6, 115.6, 104.9, 96.3, 67.9, 55.4, 46.3, 50.0, 33.5. HRMS (CI) exact mass calcd for (C20H23NO4) requires m/z 342.1705 for [M+H]+, found m/z 342.1705. [?]D =-16.9 (c=0.751, CHCl3). The enantiomeric ratio of the product was determined by HPLC analysis of the corresponding alcohol (obtained by NaBH4 reduction) using a Chiracel AD and AD guard column (10% ethanol/hexanes, 1 mL/min); R isomer tr=15.2 min, S isomer tr=24.0 min.

The synthetic route of 15799-79-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MacMillan, David W.C.; Paras, Nick A.; US2003/236438; (2003); 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. 15799-79-8, name is 3-Methoxy-N,N-dimethylaniline, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 3-Methoxy-N,N-dimethylaniline

[0092] (R)-3-(4-Dimethylamino-2-methoxy-phenyl)-pentanal (Table 1, entry 3): To a 2-dram vial equipped with a magnetic stir bar was added (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidin-4-one (24.6 mg, 0.100 mmol, 0.200 equiv), CH2Cl2 (0.50 ml), HCl (as a 4N solution in 1,4-dioxane, 25.0 uL, 0.100 mmol, 0.200 equiv), and N,N-dimethyl-m-anisidine (73.3 uL, 0.500 mmol, 1.00 equiv). The solution was cooled to -50o C. before pentenal (98.0 uL, 1.00 mmol, 2.00 equiv) was added. After 62 h, the reaction mixture was subjected directly to silica gel chromatography. Elution with 20% EtOAc in hexanes followed by concentration and removal of residual pentenal under vacuum afforded the product as a colorless oil in 68% yield (79.5 mg, 0.338 mmol); 88% ee. IR (film) 2959, 2926, 2871, 2839, 2800, 2721, 1718, 1616, 1569, 1517, 1351, 1237, 1136, 1034, 979.5, 812.9 cm-1;1H NMR (300 MHz, CDCl3) ?9.63 (t, J=2.8 Hz, 1H, CHO), 6.97 (d, J=8.2 Hz, 1H, ArH), 6.30 (dd, J=2.5, 8.3 Hz, 1H, ArH), 6.26 (d, J=2.5 Hz, 1H, ArH), 3.81 (s, 3H, OCH3), 3.40 (dt, J=7.3, 7.4 Hz, 1H, ArCH), 2.94 (s, 6H, N(CH3)2), 2.66 (dd, J=2.7, 7.4 Hz, 2H, CH2CO), 1.72-1.61 (m, 2H, CH2CH3), 0.83 (t, J=7.4 Hz, 3H, CH2CH3); 13C NMR (75 MHz, CDCl3) 203.8, 158.2, 150.6, 128.4, 119.8, 105.0, 96.5, 55.5, 49.7, 1.1, 34.9, 28.4, 12.4. HRMS (CI) exact mass calcd for (C14H21NO2) requires m/z 236.1650 for [M+H]+, found m/z 236.1649. [?]D=-18.9 (c=0.970, CHCl3). The enantiomeric ratio of the product was determined by HPLC analysis of the corresponding alcohol (obtained by NaBH4 reduction) using a Chiracel AD and AD guard column (3.0% ethanol/hexanes, 1 mL/min); S isomer tr=11.5 min, R isomer tr=12.4 min.

According to the analysis of related databases, 15799-79-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MacMillan, David W.C.; Paras, Nick A.; US2003/236438; (2003); A1;,
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Synthetic Route of 239122-51-1,Some common heterocyclic compound, 239122-51-1, name is 5-Bromo-3-fluoro-2-methoxyaniline, molecular formula is C7H7BrFNO, 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) N- (5-Bromo-3-fluoro-2-methoxy-phenyl)-2- [(E)-hydroxyiminol -acetamideIn a 500 ml three-necked flask, 2,2,2-trichloroethane-1,1-diol (8.68 g, 52.5 mmol) and sodium sulfate (47.4 g, 334 mmol) were combined with water (122 ml) to give a colorless solution. The reaction mixture was heated to 50 C and a mixture of 5-bromo-3-fluoro-2-methoxyaniline (CAS239122-51-1, 10.50 g, 47.7 mmol) in water (60 ml), dioxane (60 ml) and aqueous hydrochloricacid (7.84 ml, 95.4 mmol) were added. Then hydroxylamine hydrochloride (9.95 g, 143 mmol)in water (60 ml) was added. The reaction mixture was heated to 70 C and stilTed for 15 hoursand then cooled to room temperature. The precipitate was filtered off and washed with water (50ml) and dried in vacuo to yield the title compound as brown solid (13.4 g, 96 %). MS: mle =289.1, 291.3 [M-H].

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Bromo-3-fluoro-2-methoxyaniline, its application will become more common.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; BISSANTZ, Caterina; BONNAFOUS, Rene; BUETTELMANN, Bernd; JAKOB-ROETNE, Roland; LERNER, Christian; RUDOLPH, Markus; WO2014/102233; (2014); A1;,
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Adding a certain compound to certain chemical reactions, such as: 172282-50-7, name is 4-(Difluoromethoxy)benzene-1,2-diamine, 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 172282-50-7, SDS of cas: 172282-50-7

Preparation of Intermediate C7. Step 1 . Preparation of C7-1 : To a solution of C4-1 (1 .84 g, 10.93 mmol) and 4-(difluoromethoxy)benzene-1 ,2-diamine (1 .90 g, 10.93 mmol, prepared according to Reference Example 30y of International Patent Publication No. WO 2003/035065, p. 51 1 .) in DMF (40 mL) at rt was added DIPEA (9.5 mL, 54.65 mmol) and HATU (6.23 g, 16.4 mmol). The reaction mixture was stirred at room temperature for 24 h, diluted with ethyl acetate (100 mL), washed with water (100 mL) and brine (50 mL). The mixture was concentrated in vacuo. Purification via silica gel chromatography (EtOAc in hexanes: 20% to 60%) provided C7-1 as the later eluting fraction of two with the similar mass spectra. LCMS-ESr (m/z): [M+H]+ calcd for Ci2H9F4N2O: 289.2; found: 289.0.

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

Reference:
Patent; GILEAD SCIENCES, INC.; BJORNSON, Kyla; KARKI, Kapil K.; LINK, John O.; PYUN, Hyung-Jung; SCHRIER, Adam J.; STEVENS, Kirk L.; TAYLOR, James G.; VIVIAN, Randall W.; ZABLOCKI, Jeff; ZIPFEL, Sheila; WO2014/145095; (2014); A1;,
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Application of 1236000-51-3, A common heterocyclic compound, 1236000-51-3, name is N-Methyl-1-(4-(trifluoromethoxy)phenyl)methanamine hydrochloride, molecular formula is C9H11ClF3NO, 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.

Intermediate 28 To a solution of 1.0 g of 3-iodobenzoic acid in 20 ml of CH2CI2 under argon atmosphere was added via cannula a solution of 1.11 g of DCC in 22 ml of CH2CI2. The resulting mixture was stirred for 1 h, then was added a solution of 0.65 g of Intermediate 1 and 0.414 ml of Et3N in 13 ml of CH2CI2. The resulting mixture was stirred overnight, diluted with Et2O, filtered off and the filter cake washed with Et2O. The filtrate was washed with 10% NaHCO3 and brine, dried over MgSO4, filtered and concentrated under vacuum. The residue was purified by chromatography on silica gel eluting with EtOAc-Hex 10:90 to 50:50 to afford 1.063 g (91 %) of the title compound as a colourless oil. 1H NMR (delta, ppm, CDCI3): 7.79 and 7.75 (s, 1 H); 7.39 (s, 1 H); 7.23 (d, 2H); 7.21-7.1 1 (m, 2H); 4.72 and 4.49 (s, 2H); 3.02 and 2.88 (s, 3H). [ES MS] m/z: 436 (MH+).

The synthetic route of 1236000-51-3 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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Application of 2338-54-7, A common heterocyclic compound, 2338-54-7, name is 4-Fluoro-3-methylanisole, molecular formula is C8H9FO, 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.

The 4-fluoro-3-methylanisole (7.32 g, 52.28 mmol) was dissolved in 30 ml of carbon tetrachloride. To this solution was added N-bromosuccinimide (9.772 g, 1.05 eq) and A1 EN 428 mg, 5% eq). The mixture was refluxed for 1 hr and then cooled. The solid was filtered out and the filtrate was evaporated. The residue was extracted with ethyl acetate and washed with concentrated sodium bicarbonate. The organic layer was dried and solvents were removed to give an oil (13.0 g). The crude oil was dissolved in 150 ml of ethanol and sodium cyanide (12.8 g, 261 mmol) was added followed by the addition of water (20 ml). The mixture was refluxed for 2.5 hrs. The insoluble material was filtered out and the filtrate was concentrated. The residue was extracted with water and ether. The organic layer was dried and solvents were evaporated to give an oil (8.0 g). This oil was dissolved in 120 ml of ethanol. To that solution was added water (40 ml) and solid sodium hydroxide (20.9 g, 10.0 eq). The mixture was refluxed overnight to give a clear solution. Solvents were evaporated and the residue was suspended in 200 ml of hot water. The solution was cooled down and extracted with ether twice. The aqueous layer was acidified with 6N hydrochloric acid and then extracted with ether. The organic layer was washed with brine and dried. After the evaporation of solvents, 2-fluoro-5-methoxyphenylacetic acid was obtained (6.56 g, 68% in three steps).

The synthetic route of 2338-54-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; WO2004/101528; (2004); A2;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Synthetic Route of 13024-17-4,Some common heterocyclic compound, 13024-17-4, name is N-Methyl-3-phenoxyaniline, molecular formula is C13H13NO, 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: S7 (0.35 g, 2 mmol) was dissolved in Et2O (5 mL) and converted into its hydrochloride salt by drop-wise addition of aq. HCl (1 M) in Et2O. The resulting precipitate was collected byfiltration, dried for 10 min, and used in the subsequent reaction. A mixture of S7 hydrochloride (212 mg, 1 mmol), S1 (185 mg, 1.1 mmol), and toluene (2 mL) was heated to 130 oC,stirred for 21 h, cooled to rt, and diluted with MeOH (5 mL). This solution was concentrated onto silicagel and purified on a silica gel column with gradient elution (EtOAc EtOAc-MeOH;4: 1 v/v). The fractions containing the desired guanidine were collected, concentrated under reduced pressure, andapplied to a second silica gel column eluted with Et3N-EtOAc-hexanes(5: 20: 75 by vol.) to afford 20 asa white solid

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route N-Methyl-3-phenoxyaniline, its application will become more common.

Reference:
Article; Naumiec, Gregory R.; Cai, Lisheng; Pike, Victor W.; Bioorganic and Medicinal Chemistry Letters; vol. 25; 2; (2015); p. 225 – 228;,
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Related Products of 1036724-54-5, 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 1036724-54-5 as follows.

Six reactions were carried out in parallel and combined for work-up. To a solution of the product of the previous step (200 g, 711 mmol) in 15 THF (100 mL) was added 11 potassium carbonate (197 g, 1.4 mol). The reaction mixture was purged with nitrogen 3 times, followed by addition of Pd(dppf)Cl2-CH2Cl2 (11.6 g, 14.2 mmol). The reaction mixture was cooled to 0 C., diethylzinc (1 M, 1.07 L) was added drop-wise, and the reaction mixture was stirred at 70 C. for 1 h. The reactions were combined, cooled to 20 C. and poured into water (7 L) slowly. To the mixture was added aq. 4 M 16 HCl to pH 6. The organic layer was separated, and the aqueous phase was extracted with EtOAc (3×2 L). The combined organic layer was washed with brine (5 L), dried over sodium sulfate, concentrated, and purified through a silica gel pad (eluted with 50:1 17 petroleum ether:EtOAc)) to give the title intermediate (900 g, 92% yield) as a light yellow 18 oil. 1H NMR (400 MHz, CDCl3) delta 7.29-7.43 (m, 5H), 6.94-6.97 (m, 1H), 6.82 (d, J=8.0 Hz, 1H), 6.70 (m, 1H), 5.09 (s, 2H), 2.52-2.58 (m, 2H), 1.17 (t, J=7.6 Hz, 3H).

According to the analysis of related databases, 1036724-54-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; THERAVANCE BIOPHARMA R&D IP, LLC; FATHEREE, PAUL R.; JIANG, LAN; MCKINNELL, ROBERT MURRAY; THALLADI, VENKAT R.; ZHANG, HAO; DABROS, MARTA; NZEREM, JERRY; BENJAMIN, NOAH; KLEINSCHEK, MELANIE A.; CRATER, GLENN D.; (40 pag.)US2018/311255; (2018); A1;,
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Reference of 13985-15-4, 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. 13985-15-4 name is 2,3,6,7-Tetramethoxy-9,10-dimethylanthracene, 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.

General procedure: To a gently refluxing solution of the anthracene (1a-1c) (1mmol) in 1,2-dichloroethane (50mL) was added portionwise 5-nitrobenzenediazonium-2-carboxylate (2.5mmol). When TLC showed that the starting anthracene was consumed, the reaction mixture was concentrated under reduce pressure. The residue was purified by flash column chromatography on silica gel with petroleum ether: CH2Cl2=4:1 (v/v) as eluent to yield the triptycene as a pale yellow solid. 2b: 67mg, 15% yield. 1H NMR (300MHz, CDCl3): delta 8.08 (s, 1H), 7.87 (d, 1H, J=6.9Hz), 7.37 (d, 1H, J=8.2Hz), 6.98 (s, 2H), 6.97 (s, 2H), 3.86 (s, 12H), 2.46 (s, 3H), 2.43 (s, 3H). 13C NMR (75MHz, CDCl3): delta 156.4, 151.2, 146.3, 146.2, 145.1, 140.4, 139.9, 120.9, 120.4, 115.0, 106.2, 106.0, 56.42, 56.38, 48.5, 48.3, 13.9, 13.7. EI-TOF-MS: m/z 447 [M]+. Anal. calcd. for C26H25NO6·0.1CH2Cl2: C, 68.75; H, 5.57; N, 3.07. Found: C, 68.81; H, 5.80; N, 2.97.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2,3,6,7-Tetramethoxy-9,10-dimethylanthracene, and friends who are interested can also refer to it.

Reference:
Article; Li, Peng-Fei; Han, Ying; Chen, Chuan-Feng; Chinese Chemical Letters; vol. 26; 7; (2015); p. 839 – 842;,
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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. 126940-10-1, name is 1-Fluoro-3-(methoxymethoxy)benzene, This compound has unique chemical properties. The synthetic route is as follows., category: ethers-buliding-blocks

To a solution of n-BuLi (76.85 ml_, 192.122 mmol, 1 eq) in THF (300 ml_) was added TMEDA (29.89 ml_, 99.807 mmol, 1 .04 eq) cooled to – 78C and stirred for 1 h. 1 -Fluoro-3-(methoxymethoxy)benzene (30 g, 192.122 mmol, 1 eq) in THF (75 ml_) was added to the mixture dropwise under argon, then the reaction mass was stirred for 2 hr at -78C, followed by addition of trimethylborate at the same temperature then slowly warmed to rt and stirred for 16 h. Then the reaction mass was cooled to 0C, then 30% H202 (18 mL) solution was added slowly dropwise. The reaction mass was warmed to rt and stirred for 1 h. TLC analysis indicated formation of a polar spot. The reaction mixture was dissolved in EtOAc (300 mL) and washed with brine (2×50 mL) and water (2×50 mL). The separated organic layer was dried over Na2S04 and concentrated under reduced pressure to afford crude product; which was purified by column chromatography (silica gel, 100-200mesh) using 8% EtOAc in petroleum ether as an eluent to afford 2-fluoro-6-(methoxymethoxy)phenol (25 g, 75.55%) as a colorless oil.

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 126940-10-1.

Reference:
Patent; ONTARIO INSTITUTE FOR CANCER RESEARCH (OICR); AL-AWAR, Rima; ISAAC, Methvin; CHAU, Anh My; MAMAI, Ahmed; WATSON, Iain; PODA, Gennady; SUBRAMANIAN, Pandiaraju; WILSON, Brian; UEHLING, David; (191 pag.)WO2019/119145; (2019); A1;,
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