Tag: M.W=300-400

Synthetic Route of 103146-25-4, These common heterocyclic compound, 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, 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.

10.0g of 4-(4-fluoro-benzoyl)-3-hydroxymethyl-benzonitrile (MW: 255.25, assay: 96.7%; 37.9mmol) are dissolved in 14OmL of toluene. 7.77g of (S)-2-lambda/,lambda/-dimethylaminophenylethanol (MW: 165.24, 47.0mmol, 1.24 eq.) and 2.51g of methylboronic acid (MW: 59.86, assay: 98%, 41.1mmol, 1.08eq.) are added. The solution becomes slightly turbid and drops of water are rapidly formed. The mixture is heated to 500C. At reduced pressure (~60-70mbar) -10OmL of toluene / water are carefully removed. 10OmL of toluene are added and -10OmL of toluene / water are removed. 12OmL of toluene are added and about -2OmL of toluene / water are removed to get a solution of mixed boronate (~80mmol) in about 25OmL of solvent. The water content is below 0.1% as determined by a Karl Fischer titration. The reaction is cooled to – 65C. Within about 10-20 minutes 38.OmL of a -2M solution of dimethylaminopropyl magnesiumchloride in THF (-2 eq.) are added. Thereby, the temperature does not exceed -500C. The solution is stirred for another 30 minutes. Reaction control is performed with HPLC (ee = 90%). After complete conversion (area% 4-(4-fluoro-benzoyl)-3-hydroxymethyl-benzonitrile <2%) the reaction is worked up.2OmL of water are and 35mL of 2M aqueous H2SO4 (70mmol) are added to get a pH of -1.5 in the aqueous layer. After phase separation, the organic layer is washed once with 2OmL water, adjusted to pH 1 with 2M aqueous H2SO4. 15OmL of CH2CI2 are added to the combined aqueous layers. 7M aqueous NH3 is now added (29mL) until a pH of -9.0 is reached. After phase separation the aqueous layer is washed twice with 25mL of MED (at pH 9.0). The combined CH2CI2 layers are washed with 15mL of water. 7OmL of H2O are added. 10.7mL of 2M aqueous H2SO4 are added to adjust the pH to 6.4. After stirring for 10 minutes the layers are separated (pH 6.4). 35mL of water are added to the CH2CI2 layer. Addition of 1.5mL of 2M aqueous H2SO4 gives a pH of 6.4. After stirring for 10 minutes the layers are separated. 8OmL of CH2CI2 are added to the combined aqueous layers. Addition of 2mL of 7M aqueous RG/G-50021-BCK9987NH3 gives a pH of 6.4 (after equilibration). The layers are separated. The combined organic layers are washed with 2OmL of water. The layers are separated. The combined CH2CI2 layer contains the enantiomerically enriched diol. The combined aqueous layer contains -90% of the chiral auxiliary. 20OmL of CH2Cl2 are removed. 6OmL of 2-propanol are added. 3OmL of 2-propanol / CH2CI2 are removed under reduced pressure. 3OmL of 2-propanol are added to obtain -13g of CIT-DIOL in 6OmL of ISO. To this solution 6.59g of (+)-ditoluoyl tartaric acid (MW: 386.36; assay: 99%; 17.1mmol, 0.45eq.), dissolved in 42mL of 2-propanol and 8mL of CH2CI2, are added. The product starts to crystallize after 5 minutes (or immediately after seeding). The mixture is stirred for 90 minutes at 35C, for 10 minutes at 600C and than slowly cooled down to room temperature (within ~5hours) and crystallized without stirring for 10 hours. The product is isolated by filtration to give 17.2g of S-CIT-DIOLlambda’ (+)-DTTA.lambda1 ISO.lambda1 H2O (yield: 81.0%; ee: 99.0%, assay: 61.0%) after drying for IOhours at 400C and 20mbar.

Statistics shows that 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile is playing an increasingly important role. we look forward to future research findings about 103146-25-4.

Reference:
Patent; SANDOZ AG; WO2007/82771; (2007); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Synthetic Route of 103146-25-4, A common heterocyclic compound, 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, molecular formula is C20H23FN2O2, 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.

Example 1 50 GMS OF 4- [4- (DIMETHYLAMINO)-1- (4 -FLUOROPHENYL)-1-HYDROXYBUTYL]-3 (HYDROXYMETHYL) – benzonitrile (cyano diol) was added to a mixture of 50 gm phosphoric acid and 150 gm water. The mixture was heated to 105C for 14 hours. The reaction mixture was cooled to 40C and diluted with 1000 ml water. The pH of the solution was adjusted to 8-10 with liquor ammonia and extracted with ethyl acetate. The ethyl acetate layer was washed with 50 ML of 5% disodium edetate solution twice to remove the carboxamide impurity (about 3%) and the cyano diol impurity (about 0.8%). The ethyl acetate layer was dried over sodium sulphate, treated with decolorizing charcoal and filtered. The solution was acidified to a pH between 3-3.5 with 48% aqueous hydrobromic acid. The precipitated product of citalopram hydrobromide was filtered. This product had a purity of greater than 99.85%.

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; MEDITAB SPECIALITIES PVT. LTD; WAIN, Christopher, Paul; WO2005/12278; (2005); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, belongs to nitriles-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 103146-25-4, Product Details of 103146-25-4

Oxalate [(+-)-Diol Oxalate Salt] (+-)-Diol compound (VI) (360 g, 1.05 mol) was dissolved in ethanol (1400 ml) and heated to 50-55 C. to obtain a clear solution. Oxalic acid dihydrate (164.40 g, 1.3 mol) was added slowly and cooled the obtained solution to 15-20 C. and stirred for 4 hrs to complete the crystallization. Product formed was filtered and dried at 50-60 C. under vacuum to yield 360 g of Diol oxalate salt (VIa), with HPLC purity of 99.95%. (Melting Range: 168-171 C.) 1H NMR (DMSO-d6) delta ppm: 7.89-7.09 (m, 7H), 5.54 (d. 1H), 4.03 (d, 1H), 2.98-2.94 (m, 2H), 2.63 (s, 6H), 2.32-2.15 m, 2H), 1.6-1.3 (m, 2H) IR (KBr, cm-1):

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Reference:
Patent; Kaushik, Vipin Kumar; Mohammed, Umar Khan; Meenakshisunderam, Sivakumaran; US2009/99375; (2009); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, belongs to nitriles-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 103146-25-4, Quality Control of 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile

A, To 40g citalopram diol intermediate free alkali crystal prepared in Example 1 (purity: 99.9%, HPLC, area normalization method), 360ml isopropanol was added and the solution was heated until the crystal was dissolved entirely. 23.6g D-di-4-methylbenzyol tartaric acid was added and dissolved, the solution was placed at room temperature for 12 hours. The crystal crystallized and was filtrated, washed with small amount of isopropanol to give S-citalopram diol intermediate—D-di-4-methylbenzyol tartaric acid salt crystal. The obtained salt was then suspended and mixed in toluene, added with NaOH solution and stirred. The solution was placed aside, the organic and inorganic layer was separated. The toluene layer was heated, concentrated under vacuum to give 14g S-citalopram diol intermediate oil substance (yield: 70%, purity: 99.9%), in which there was 0.5% R-citalopram diol intermediate (chiral HPLC).

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; Hangzhou Minsheng Pharm. Co., Ltd.; EP1700851; (2006); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Application of 103146-25-4, 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 103146-25-4 as follows.

Experiment 38. A range of experiments were conducted examining the resolution of diol with (+)- (S,S)-DTT. The general procedure is described below, and the details and results for each reaction are in table 1.Racemic diol (20 g, 58.4 mmol) was dissolved in approximately half of the solvent used for the experiment at 40 0C. (-H)-(S5S)-DTT-H2O (quantity specified in the table) was added as a solution in the other half of the solvent. The solution was held at 40 0C and was seeded within two minutes with crystals of (S)-diol. ./2(-H)-(S5S)-DTT (approximately 5 mg). Crystallisation typically began within 5-10 minutes after seeding. After 2 h at 40 0C, the temperature of the solution was lowered to 20 0C over 2 h, and the solution was held at this temperature for a further 1 h. The product was then separated by filtration, washed with the approriate solvent (2 x 20 mL) and dried overnight at 60 0C under reduced pressure.

According to the analysis of related databases, 103146-25-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; H. LUNDBECK A/S; WO2009/33488; (2009); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Application of 103146-25-4, 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. 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, This compound has unique chemical properties. The synthetic route is as follows.

A test tube equipped with a stopper was charged with 10 mg (0.029 m mol) of [(=T :)-4-] [4-dimethylamino-1- (4′-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile, 10 mg of Novozym 435 (product of NOvozymes), 33 mg (0.29 [M MOL)] of vinyl butyrate and 1 ml of various kinds of solvents, and stirred at [30C] for 16 hours. After the reaction, converted ratios and optical purities were analyzed and E-values were calculated. The results are shown in Table 9.

The chemical industry reduces the impact on the environment during synthesis 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; H. LUNDBECK A/S; WO2004/14821; (2004); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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. 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, A new synthetic method of this compound is introduced below., Safety of 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile

Process for the preparation of citalopram (by double Grignard method): A solution of 4-fluorophenyl magnesium bromides prepared from 153. 33g 4-flour bromobenzene (0.876 moles) and 25.33g magnesium turnings (1. 055 moles) and iodine (0.05gm) in dry 300mi tetrahydrofuran was added to a suspension of 100g 5- cyanophthalide (0.628 moles) in 900ml dry methylene dichloride at-4 to-2C. After the completion of the reaction a solution of 3-N, N dimethylaminopropyl magnesiumchloride in toluen/THF mixture [generated in situ by reacting 175g 3-N, N dimethylamiopropyl chloride (1. 446mole) in 350ml toluene with 41. 6gm magnesium turnings (9. 733moles) and iodine (0. 05g) in dry 75ml tetrahydrofuran and dibromoethane] was added between 0- 5C. The reaction mass was then maintained at-5 to 0C for 3-4 hours. After completion of the reaction, the reaction mass was quenched with 200ml 20% aqueous ammonium chloride solution. The toluene layer was separated and washed with 200ml water. Methylene dichloride and THF was distilled. 189g sulphuric acid and 60ml of water was added to the toluene layer and heated to 85-90C. The same temperature was maintained for additional 4-5 hours. After completion of the reaction the reaction mass was diluted with 200ml water and the pH was adjusted to basic with liquor ammonia below 10-15C. The toluene layer was separated, washed with 200moi water and extracted with 400ml 20% acetic acid (80mi acetic acid and 320ml water). The aq. acid extract was cooled to 5- 10C and the pH was adjusted to 8.5 to 9.0 using liquor ammonia (85ml) at 5-10C and extracted with toluene 3x600m1. The toluene layer was washed with water, dried over anhydrous sodium sulphate. The dried toluene layer was treated with carbon (10g) and filtered. The filtrate toluene was subjected to salt formation in accordance with the following methods:

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; JUBILANT ORGANOSYS LIMITED; WO2005/77927; (2005); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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. 906673-45-8, name is 4-(4-Bromo-3-(hydroxymethyl)phenoxy)benzonitrile, A new synthetic method of this compound is introduced below., Recommanded Product: 906673-45-8

Compound IV (1.00 g, 3.3 mmol, 1.0 eq) was dissolved in DMF (15 mL), 60% sodium hydride (0.16 g, 4.0 mmol, 1.2 eq) was added, and stirred at room temperature for 30 min. 2,3,4-Trimethoxybenzyl chloride (1.00 g, 4.6 mmol, 1.4 eq) was added, and the reaction was stirred by heating to 85 C. After 6h, TLC showed that the basic reaction of the raw materials was completed, post-processing was carried out, and the reaction solution was cooled to room temperature. The reaction mixture was quenched by adding 20 mL of water, extracted with 50 mL EA, liquid separation was carried out, the organic phase was washed, dried, concentrated and the crude product was purified by column chromatography to give 1.46 g of yellow oil. That is, the target compound, the yield was 76%.

The synthetic route of 906673-45-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Suzhou Wangshanwangshui Bio-pharmaceutical Co., Ltd.; Chinese Academy Of Sciences Shanghai Pharmaceutical Institute Suzhou Pharmaceutical Chuangxin Institute; Shandong Tefaman Pharmaceutical Co., Ltd.; Tian Guanghui; Wu Jianzhong; Yu Jianghui; Pang Zhenqiang; Li Junyong; (10 pag.)CN108047261; (2018); A;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 103146-25-4,Some common heterocyclic compound, 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, molecular formula is C20H23FN2O2, 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.

In a 200-ml four-necked flask equipped with a stirrer and a thermometer, 1.5 g [(4.] [38] m mol) of [()-4- [4-DIMETHYLAMINO-1- (4′-FLUOROPHENYL)-1-HYDROXYBUTYL]-3-] hydroxymethylbenzonitrile was dissolved in 30 ml of toluene, then 0.45 g of Novozym 435 (product [OF NOVOZYMES),] 0.347 g (4.38 m mol) of pyridine, 4.38 m mol of various kinds of acids and 1.00 g (8.76 m mol) of vinyl butyrate were added, and stirred at [40C] for between 16 and 21.5 hours. The result is shown in Table 4. Example 6 In a 200-ml four-necked flask equipped with a stirrer and a thermometer, 3.0 g [(8.] 76 m mol) of [( : L)-4- [4-DIMETLIYLAMINO-L- (41-FLUOROPHENYL)-L-HYDROXYBUTYL]-3-] hydroxymethylbenzonitrile was dissolved in 30 ml of toluene, then 0.9 g of Novozym [435] (product [OF NOVOZYMES),] 0.693 g (8.76 m mol) of pyridine, 8.76 m mol of various kinds of acids and 2.00 g (17.52 m mol) of vinyl butyrate were added, and stirred at [40C] for between 15.5 and 16.5 hours. The results are shown in Table 5.

The synthetic route of 103146-25-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; H. LUNDBECK A/S; WO2004/14821; (2004); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

These common heterocyclic compound, 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, 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. Application In Synthesis of 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile

EXAMPLE 4 (+-)-Diol compound (VI) (7 g, 0.0205 mol) and oxalic acid dihydrate (2.96 g, 0.0235 mol) were added to n-butanol (77 ml) and the contents were heated to 80-85 C. to obtain a clear solution. Obtained solution was cooled slowly to 15-20 C. and stirred for 3 h to complete the crystallization. The product formed was filtered and washed with n-butanol (2*7 ml). Thereafter, product was dried at 50-60 C. under reduced pressure to give 8.5 g of diol oxalate salt (VIa), with HPLC purity of 99.93%.

The synthetic route of 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Kaushik, Vipin Kumar; Mohammed, Umar Khan; Meenakshisunderam, Sivakumaran; US2009/99375; (2009); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts