Category: 366-99-4

Reference of 366-99-4, 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. 366-99-4, name is 3-Fluoro-4-methoxyaniline belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Example 4a (see general route 4, procedure H, M and K)2-(3-fluoro-4-methoxyphenyl)hydrazine; [00257] A room temperature solution of 3-fluoro-4-methoxyaniline (25.0 g, 177 mmol) in concentrated 12M aqueous hydrochloric acid solution (60 mL) was stirred for two hours, after which it was cooled to 0°C to which a solution of sodium nitrite (14.2 g, 205 mmol), in water (50 mL), was added, drop-wise over 45 minutes, with internal temperature monitoring such that the reaction temperature does not warm above 5°C. After stirring for one hour at 0°C, the reaction mixture was poured slowly into a 0°C pre-made solution of tin(II) chloride dihydrate (168 g, 744 mmol) in concentrated 12M aqueous hydrochloric acid solution (125 mL). The reaction mixture was allowed to warm up to room temperature, after which it was stored in the freezer overnight (12 hours), leading to the formation of a precipitate. This dark brown solid was successively washed with water (2 x 100 mL) and diethyl ether (3 x 100 mL), and dried to afford crude 2-(3-fluoro-4-methoxyphenyl)hydrazine hydrochloride as a pasty brown solid (note that this crude solid can also be used directly in the next step). As part of the purification and isolation process, the crude hydrazine hydrochloride salt was reconstituted in water (100 mL) and 3M aqueous sodium hydroxide solution (200 mL), extracted with diethyl ether (2 x 200 mL), washed with successively with saturated sodium bicarbonate solution (2 x 100 mL), water (2 x 20 mL) and saturated sodium chloride solution (2 x 20 mL), dried (sodium sulfate), filtered and concentrated to afford 2-(3-fluoro-4- methoxyphenyl)hydrazine as a light yellow solid (15.0 g, 96.1 mmol, 54percent yield. 1H NMR (400 MHz, CDC13) delta (ppm): 6.87 (m, 1H), 6.66 (dd, 1H), 6.49-6.53 (m, 1H), 5.06 (br. s, 1H), 3.83 (s, 3H), 3.55 (br. s, 2H).[00258] A portion of 2-(3-fluoro-4-methoxyphenyl)hydrazine (5.00 g, 32.0 mmol) was dissolved in absolute ethanol (50 mL), to which a solution hydrogen chloride (15 mL, 2.5M in ethanol) was added. The resulting precipitate was filtered, washed with ethyl acetate (2 x 40 mL), and dried to afford 2-(3-fluoro-4-methoxyphenyl)hydrazine hydrochloride as an off- white solid (4.7 g).

The synthetic route of 3-Fluoro-4-methoxyaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; IRONWOOD PHARMACEUTICALS, INC.; HUDSON, Colleen; BARDEN, Timothy, C.; JIA, James; MERMERIAN, Ara; PENG, Bo; YANG, Jane; YU, Xiang, Y.; SPROTT, Kevin; WO2012/88469; (2012); A1;,
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366-99-4, name is 3-Fluoro-4-methoxyaniline, 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. Computed Properties of C7H8FNO

Cyanuric chloride (11.07 g, 60 mmol) was dissolved in 40 mL CH3CN and was cooled to about -20° C. To this was added DIEA (11.5 mL, 60 mmol) followed by 3-fluoro-4-methoxyaninline (8.47 g, 60 mmol) in 20 mL CH3CN (reaction froze). The reaction was allowed to warm to room temperature after about 1 hour at -20° C. TLC (2percent CH3OH/CH2Cl2) and mass spectroscopy indicated the presence of the compound 124. The reaction mixture was cooled to about 0° C. before adding DIEA (11.5 mL, 66 mmol). 2-Aminomethyl-1-ethylpyrrolidine (7.77 g, 60 mmol) in CH3CN (10 mL) was added. The reaction was allowed to warm to rt and stirred overnight. Then DIEA (11.5 mL, 66 mmol) and S-(+)-2-methoxyethylpyrrolidine (6.91 g, 60 mmol) in 20 mL 1,4-dioxane were added. The reaction was heated at about 50° C. overnight. The solvent was removed in vacuo, and the resulting residue was purified by flash chromatography on silica gel packed in ethyl acetate. The front running impurities were removed and subsequently the eluent was increased in polarity to 10percent CH3OH:ethyl acetate. The material collected from the column was then dissolved in water and extracted in CH2Cl2 (4 times), dried over MgSO4, and concentrated to dryness to give a brown solid 145 (9.7 g, 27.6percent yield), 71-72° C.; HPLC: Inertsil ODS-3V C18, 40:30:30 [KH2PO4 (0.01M, pH 3.2):CH3OH:CH3CN], 264 nm, Rt 5.37 min, 90.3percent purity; 1H NMR (600 MHz, CDC3, 55° C.) delta 7.69 (s, 1H), 7.08 (d, J=7.8 Hz, 1H), 6.86 (t, J=9 Hz, 1H), 4.29 (s, 1H), 3.90-3.96 (m, 1H), 3.84 (s, 3H), 3.63-3.81 (m, 6H), 3.35 (s, 3H), 3.23-3.25 (m, 1H), 2.85 (broad s, 1H), 2.78 (broad s 1H), 2.14 (broad s, 2H), 1.89-2.04 (m, 6H), 1.37 (apparent t, J=7.2 Hz, 3H); 13C NMR (150.8 MHz, CDCl3, 55° C.) delta 165.8, 163.8 (2C), 152.3 (d, Jc-f=243.5 Hz), 143.0 (142.9, rotamer or diastereumer), 133.7 (133.67, rotamer or diastereomer), 115.0, 114.4, 109.1 (108.9, rotamer or diastereomer), 72.8, 66.6, 59.0, 57.0, 56.6, 53.7, 51.0, 46.8, 42.2, 28.4 (28.2, rotamer or diastereomer), 23.1 (23.0, rotamer or diastereomer), 10.9; MS (ESI) mn/z 460.2 (M+H, 44.7), 251.1 (47.7), 235.1 (27.5), 231.1 (37.4), 230.6 (100), 214.6 (36.5).

The synthetic route of 366-99-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Timmer, Richard T.; Alexander, Christopher W.; Pillarisetti, Sivaram; Saxena, Uday; Yeleswarapu, Koteswar Rao; Pal, Manojit; Reddy, Jangalgar Tirupathy; Krishma Reddy, Velagala Venkata Rama Murali; Sesila Sridevi, Bhatlapenumarthy; Kumar, Potlapally Rajender; Reddy, Gaddam Om; US2004/209882; (2004); A1;,
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366-99-4, 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. 366-99-4, name is 3-Fluoro-4-methoxyaniline belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Preparation 66A: 4-Bromo-3-fluoro-N-(3-fluoro-4- methoxyphenyl)benzenecarboximidamide To a solution of EtMgBr (48 mL, 42.55 mmol, 0.9 M) in THF (24 mL) was added a solution of 3-fluoro-4-methoxyaniline (3 g, 21.28 mmol) in THF (30 mL) at r.t. The mixture was stirred for 30 min at r.t. A solution of 4-bromo-3-fluorobenzonitrile (4.657 g, 23.40 mmol) in THF (20 mL) was added dropwise at r.t. and stirred overnight at r.t. LC/MS showed the reaction was completed, H20 was added and extracted with EA, dried, concentrated and purified by flash chromatography on silica gel (PE/EA=3/1 to EA) to afford 4-bromo-3-fluoro-N-(3-fluoro-4-methoxyphenyl)benzenecarboximidamide (4.68 g, 65percent). [M+H] Calc’d for Ci4HnBrF2N20, 341; Found, 341.

The synthetic route of 3-Fluoro-4-methoxyaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; QUANTICEL PHARMACEUTICALS, INC.; CHEN, Young, K.; KANOUNI, Toufike; NIE, Zhe; STAFFORD, Jeffrey, Alan; VEAL, James, Marvin; (166 pag.)WO2016/4105; (2016); A1;,
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366-99-4, 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. 366-99-4 name is 3-Fluoro-4-methoxyaniline, 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.

Example 18 Synthesis of (4-Chloro-6-cyclohexylmethoxy-[1,3,5]triazin-2-yl)-(3-fluoro-4-methoxy-phenyl)-amine (114) To a sample of 113 (1.011 g, 3.8 mmol) dissolved in acetone (20 mL) was added a solution of 3-fluoro-p-anisidine (0.541 g, 3.8 mmol) in acetone (10 mL) followed by addition of NaOH (1.52 mL, 2.5 N, 3.8 mmol) and water (3 mL). The reaction mixture was allowed to stir at reflux for about 3 hours under nitrogen. The reaction mixture was extracted 3 times with dichloromethane; the combined organic layers were washed with brine solution and dried over potassium carbonate. The sample was concentrated on a rotary evaporator and the resulting oil was dried overnight under vacuum. Column chromatography (silica gel, 70:30 hexanes:ethyl acetate) yielded light yellow solid compound 114 (0.581 g, 42percent), mp 98° C.; TLC (silica gel, 30:70 ethyl acetate:hexanes), Rf 0.36; MS (ESI): m/z 369 (39.1), 368 (22.1), 367 (M+H, 100), 273 (3.2), 271 (10.7). Example 19 Synthesis of 6-Cyclohexylmethoxy-N,N’-bis-(3-fluoro-4-methoxy-phenyl)-1,3,5-triazine-2,4-diamine (115) [0741] Compound 115 was obtained as a by-product (0.159 g) via column chromatography (silica gel, 70:30 hexanes:ethyl acetate), mp 181° C.; TLC (silica gel, 30:70 ethyl acetate:hexanes), Rf 0.17; MS (ESI): m/z 472 (M+H, 100), 261 (1.5).

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; Timmer, Richard T.; Alexander, Christopher W.; Pillarisetti, Sivaram; Saxena, Uday; Yeleswarapu, Koteswar Rao; Pal, Manojit; Reddy, Jangalgar Tirupathy; Krlshna Reddy, Velagala Venkata Rama Murali; Sridevi, Bhatlapenumarthy Sesha; Kumar, Potlapally Rajender; Reddy, Gaddam Om; US2004/209880; (2004); A1;,
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Application of 366-99-4, 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 366-99-4 as follows.

2-pentanone (17.2 g, 200 mmol), Acetic acid (1.8 g, 30 mmol), and Sodium triacetoxyborohydnde (6.36 g, 30 mmol) were added to a solution of 3-Fluoro-4-methoxyaniline (2.82 g, 20 mmol) in DCM (120 mL) and the mixture was stined at RT for 12 hr. Water was added to quench the reaction and the mixture was extracted with DCM. The solvent was removed under and the residue was purified by silica gel chromatography to afford 3-Fluoro-4-methoxy-N-(pentan-2-yl)aniline(2.1 g, 50percent yield). MS m/z=212 [M+H].

According to the analysis of related databases, 366-99-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; JIANGSU ASCENTAGE BIOMED DEVELOPMENT INC.; CHEN, Jianyong; ZHOU, Yunlong; WANG, Shaomeng; GUO, Ming; YANG, Dajun; JIAO, Lingling; JING, Yu; QIAN, Xu; LIU, Liu; BAI, Longchuan; YANG, Chao-Yie; MCEACHERN, Donna; WO2015/127629; (2015); A1;,
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Reference of 366-99-4,Some common heterocyclic compound, 366-99-4, name is 3-Fluoro-4-methoxyaniline, molecular formula is C7H8FNO, 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 62; Synthesis of N,N’-dicyclopropyl-N-(3-fluoro-4-methoxy-phenyl)-1,3,5-triazine-2,4,6-triamine (157); To cyanuric chloride (0.368 g, 2 mmol) in CH3CN at about -20° C. was added 3-fluoro-p-anisidine (0.28 g, 2 mmol) in CH3CN followed by the addition of DIEA (0.39 mL, 2.2 mmol) and stirred for about I hour. The reaction mixture was then stirred at room temperature for about 1 hour. Then cyclopropylamine (1.39 mL, 20 mmol) and DIEA (0.39 mL, 2.2 mmol) were added and the reaction mixture was stirred overnight at rt. The reaction mixture was worked up as usual, diluted with ethyl acetate and washed with brine. The organic layer was separated and dried over sodium sulfate, filtered, concentrated under reduced pressure, and compound 157 was purified by silica gel column chromatography (200 mg, 30percent), mp 91-92° C.; HPLC: Inertsil ODS-3V C18, 40:30:30 [KH2PO4 (0.01 M, pH 3.2):CH3OH:CH3CN], 264 nm, Rt 8.6 min, 99.1percent purity; MS (ESI): m/z 331(M+H, 100), 305 (0.8), 151 (0.3).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Fluoro-4-methoxyaniline, its application will become more common.

Reference:
Patent; Timmer, Richard T.; Alexander, Christopher W.; Pillarisetti, Sivaram; Saxena, Uday; Yeleswarapu, Koteswar Rao; Pal, Manojit; Reddy, Jangalgar Tirupathy; Krlshna Reddy, Velagala Venkata Rama Murali; Sridevi, Bhatlapenumarthy Sesha; Kumar, Potlapally Rajender; Reddy, Gaddam Om; US2004/209880; (2004); 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. 366-99-4, name is 3-Fluoro-4-methoxyaniline, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C7H8FNO

Under room temperature, will 3-fluoro-4-anisidine (21.0 g, 0 . 15 mol) adding water in (100 ml). To the stirring mixture of lowering the temperature to -5 to 0 °C. To the obtained sequentially adding in a mixture of concentrated hydrochloric acid (45 ml), sodium nitrite solution (70 ml), 2-chloro-3-oxo butyric acid ethyl ester (24.7 g, 0 . 15 mol) of ethanol solution (150 ml) and sodium acetate (36.9 g, 0 . 45 mole) aqueous solution (150 ml). After the completion of the dropping, the obtained mixture of low-temperature stirring 0.5 hours. Furthermore, the obtained mixture to room temperature, stirring for 6 hours, a solid precipitated in the reaction process. After the completion of the reaction, the obtained by filtering the mixture. The filter cake obtained by vacuum drying, the silica gel column chromatography (PE:EA=10:1) product is obtained by purification of 36.5 g (yield: 88.6percent).

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 366-99-4.

Reference:
Patent; CSPC Weisheng Pharmaceutical Technology (Shijiahuang) Co., Ltd.; Shi, Ying; Gao, Qingzhi; Mi, Yi; Wang, Xuliang; (129 pag.)CN105384739; (2016); A;,
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Related Products of 366-99-4, 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 366-99-4 as follows.

Step A: Preparation of 2-amino-N-(3-fluoro-4-methoxyphenyl)benzamide: To a stirred suspension of isatoic anhydride (1.63 g, 10 mmol) in 15 mL dioxane at room temperature under nitrogen was added powdered sodium hydroxide followed by 3-fluoro-4-methoxyaniline (1.41 g, 10 mmol). The mixture was immersed in a room temperature oil bath and slowly heated to reflux. Carbon dioxide gas evolution was evident. After stirring at reflux for 2 hours, the reaction mixture was cooled to room temperature and inorganics were filtered off with dioxane. The filtrate was concentrated to dryness to a brown solid. The crude product was dissolved in a minimum of hot 95% EtOH and crystals formed upon cooling. The crystals were filtered off and rinsed with a minimum of ice cold 95% EtOH to give a tan solid (1.0 g, 39%). 1H-NMR (400 MHz, CDCl3) delta 7.66 (br s, 1H), 7.50 (dd, 1H), 7.44 (dd, 1H), 7.26 (m, 1H), 7.17 (m, 1H), 6.95 (m, 1H), 6.71 (m, 2H), 5.50 (br s, 2H), 3.89 (s, 3H).

According to the analysis of related databases, 366-99-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Blake, James F.; Boyd, Steven Armen; De Meese, Jason; Fong, Kin Chiu; Gaudino, John J.; Kaplan, Tomas; Marlow, Allison L.; Seo, Jeongbeob; Thomas, Allen A.; Tian, Hongqi; Cohen, Frederick; Young, Wendy B.; US2007/238726; (2007); A1;,
Ether – Wikipedia,
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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. 366-99-4, name is 3-Fluoro-4-methoxyaniline, This compound has unique chemical properties. The synthetic route is as follows., name: 3-Fluoro-4-methoxyaniline

3-Fluoro-4-methoxyaniline (1, R1 = H, R2 = CH3, R3 = F) (95 g, 0.67 mol) was added to concentrated hydrochloric acid (250 mL), the suspension was stirred at ambient temperature for 18 hours, then it was cooled to 0 0C and a solution of sodium nitrite (53.7 g, 0.78 mol) in water (200 mL) was added dropwise at 0-5 0C. When the addition was complete, the resulting solution was stirred at 0 0C for 1 hour then it was added dropwise at 0-5 0C to a stirred solution of tin (II) chloride dihydrate (638.9 g, 2.83 mol) in concentrated hydrochloric acid (500 mL). The mixture was allowed to warm to ambient temperature then it was stored at 4 0C for 18 hours. The resulting precipitate was collected by filtration, washed with water (400 mL), and ether (1000 mL) and dried in vacuo. The solid hydrochloride salt was basifed by addition to 10percent aqueous sodium hydroxide solution (800 mL), the free base was extracted into ether (2 X 400 mL), and the combined extracts were dried (MgSO4) and the solvent removed in vacuo to give (3- fluoro-4-methoxyphenyl)hydrazine (2, R1 = H, R2 = CH3, R3 = F) (51.9 g, 50percent) as a yellow solid, mp 46-50 0C; 1HNMR (CDC13/25O MHz): 1.5 (s, IH, NH-NH2), 3.85 (s, 3H, OCH5), 5.0 (s, 2Eta, NH-NH2), 6.44 (m, 1Eta, phenyl 6-H), 6.60 (dd, 1Eta, phenyl 5-H), 6.79 (t, 1Eta, phenyl 2-H)-

According to the analysis of related databases, 366-99-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MICROBIA, INC.; WO2007/22501; (2007); A2;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Related Products of 366-99-4, 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. 366-99-4, name is 3-Fluoro-4-methoxyaniline belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

General procedure: To a solution of the amine (10.05mmol) in isopropanol (20ml) was added N,N-diisopropylethylamine (1.55g, 12mmol) and 2,4,5-trichloropyrimidine (1.84g, 10mmol). The reaction mixture was reflux for 2h followed by cooling to room temperature. Water (100ml) was added and the mixture was stirred for 30min. Then the mixture was filtrated. The solid was dried to provide the title compound 2a-2u.

The synthetic route of 3-Fluoro-4-methoxyaniline has been constantly updated, and we look forward to future research findings.

Reference:
Article; Chen, Hong; Li, Ridong; Ning, Xianling; Zhao, Xuyang; Jin, Yan; Yin, Yuxin; European Journal of Medicinal Chemistry; vol. 178; (2019); p. 141 – 153;,
Ether – Wikipedia,
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