Tag: M.W:800-900

Triphenyl methyl olmesartan, A common heterocyclic compound, 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.”144690-92-6

To 12.0g (15 mmol) of tritylolmesartan medoxomil prepared according to examples 1 or 2 69 ml of ethyl acetate was added and after that 12 ml of methanol and 2.67 ml (32 mmol) of conc. HCl were added. The mixture was stirred at room temperature for 2h and then the mixture was cooled to below 2C. To the cooled mixture 71 ml of 1% NH3 was slowly added to adjust pH to 4.93. The phases were separated and water phase was reextracted with 20 ml of ethyl acetate. Collected organic phases were dried over Na2SO4, filtered and concentrated under reduced pressure to approximately 15g of oily residue. To this residue 15 ml of ethyl acetate were added and the mixture was cooled to 20 C and stirred at this temperature for 2h, and then cooled under 0C and stirred at this temperature for 1hour. The product was filtered off and washed with 5 ml of fresh ethyl acetate and dried. Yield: 7.55 g (90%). HPLC: 99.81 % of the product, all individual impurities under 0.10%.

The chemical industry reduces the impact on the environment during synthesis, Triphenyl methyl olmesartan, , I believe this compound will play a more active role in future production and life.

Reference£º
Patent; Krka Tovarna Zdravil, D.D., Novo Mesto; EP2334668; (2011); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

144690-92-6, A common heterocyclic compound, 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.”144690-92-6

Example 2; 36.0 g (50.3 mmol) ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-(4-[2-(trityltetrazol-5-yl)-phenyl]phenyl}-methyl imidazole-5-carboxylate (Va) and 3.0 g (75.4 mmol) of NaOH were suspended in 413 ml dimethylacetamide. The suspension was then stirred at room temperature for 20 h and after that 6.9 g (50.3 mmol) of K2CO3 were added. The mixture was cooled to 0C and solution of 15.4 g (70.4 mmol) 4-chloromethyl-5-methyl-2-oxo-1,3-dioxolene in 39 ml of dimethylacetamide were slowly added. The mixture was slowly heated to 50C and stirred at this temperature for 2 h. After esterification was completed, the mixture was cooled to 10 C and poured into a mixture of 625 ml of ethyl acetate and 625 ml of 10 % NaCl, and stirred at 25 C for 15 min. The phases were separated and organic phase was washed 2x with 500 ml of 10 % NaCl, dried over Na2SO4 and filtered. The filtrate was concentrated up to ? (approximately 270 g) at reduced pressure. To the resulting solution, 80 ml of ethanol and 8.3 ml (100 mmol) of conc. HCl were added and stirred at 24-26C for 3h. To the cooled mixture 600 ml of water was added and pH of the suspension was estimated to 5 by addition of 5 M NaOH. The phases were stirred for 15 min and separated. Water phase was reextracted with 150 ml of ethyl acetate. Collected organic phases were dried over Na2SO4, filtered and concentrated under reduced pressure. 560 ml of ethyl acetate were added and the mixture was evaporated again. After that, 300 ml of ethyl acetate were added and the mixture was cooled to 20 C and stirred for 1h, filtered off and washed with 20 ml of fresh ethyl acetate. The yield of the product (I) was 21 g (75 %)., 144690-92-6

As the rapid development of chemical substances, we look forward to future research findings about 144690-92-6

Reference£º
Patent; KRKA, tovarna zdravil, d.d., Novo mesto; EP1816131; (2007); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

144690-92-6, A common heterocyclic compound, 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.”144690-92-6

Example 2: preparation of olmesartan medoxomil (I) as per the present invention: To a mixture of acetic acid ( 37.5 ml) and water (12.5 ml) was added trityl olmesartan medoxomil (III) (10 g) and heated at 40-45 C for 2 hours. Water (12.5 ml) was added and the reaction mixture was filtered to remove trityl alcohol. The filtrate was subjected to agitated thin film dryer, wherein the feed rate was of about 4 to 10 ml per minute, heating medium was jacketed hot water at 45-50 C and vacuum was 70-75 mm/Hg. Crude olmesartan medoxomil (I) was recovered form ATFD. HPLC purity: olmesartan medoxomil (I) (97.81 %); olmesartan acid impurity (II) (0.97%). To acetone (40 ml) crude olmesartan medoxomil (I) was added, the slurry was heated at 54-58 C for 30 minutes and then stirred for 1 -2 hours at 0-5 C, the solid was filtered. Wet solid was added to acetone (120 ml) and heated at 55-60C. The solution was filtered. From the filtrate about 95 ml of acetone was distilled out at atmospheric pressure. The concentrated mass was stirred at 25-30 C for 8-12 hours and then at 0-5 C for 1 -3 hours. The solid was filtered, washed with acetone and dried. Yield 5.3 g (76.81 %). HPLC purity: olmesartan medoxomil (I) (99.67 %); olmesartan acid impurity (II) (0.07%).

The chemical industry reduces the impact on the environment during synthesis, Triphenyl methyl olmesartan, , I believe this compound will play a more active role in future production and life.

Reference£º
Patent; LUPIN LIMITED; FIRKE, Rajendra, Viswanath; SISODIA, Ujjwal,Komalsingh; BHANGALE, Chandrakant,Shriram; SHIVDAVKAR, Radhakrishna, Bhikaji; GODBOLE, Himanshu, Madhav; SINGH, Girij, Pal; WO2013/21312; (2013); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

144690-92-6, A common heterocyclic compound, 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.”144690-92-6

10L reaction flask was charged 500.0g (0.62mol) compound 6,3L water, 1L of acetone, was added dropwise a solution of 645.0g of 22.5% sulfuric acid at 20 . Dropping was completed, the reaction at room temperature after 4.5h TLC or HPLC in control, raw reaction was complete. Body cooling system to 0-5 , when the temperature stabilized filtrate back into the reaction vessel was charged with acetone 1L and 2L water. The system was maintained at 15 solution of 210g of potassium carbonate and 400g water to form a solution, drops of completion, stirring after 1-2h incubation filtration. The filter cake was dried to obtain olmesartan medoxomil pure 328.9g. HPLC: 99.96%, yield: 94.3%, 144690-92-6

As the rapid development of chemical substances, we look forward to future research findings about 144690-92-6

Reference£º
Patent; Jiangsu Bang Pharmaceutical Co., Ltd.; Zhao, Guangrong; Huan, Shuang; Zhao, Huayang; Liu, Liping; Chen, Guoping; Tang, Jingyu; (19 pag.)CN105481842; (2016); A;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

144690-92-6, A common heterocyclic compound, 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.”144690-92-6

7.5 cm in diameterIn a 500 mL four-necked flask equipped with two stirring blades,40 g of trityl olmesartan medoxomil,180 ml of acetic acid,40 g (1.0 volume) of water was added,The mixture was stirred at 40 C. for 2 hours to carry out deprotection reaction (reaction conversion: 98.4%Olmesartan medoxomil purity: 98.95%,Olmesartan dimer: 0.047%).Then,The reaction solution was cooled to 20 C.,80 g of water was added,After stirring at 20 C. for 1 hour,The precipitated triphenylmethanol was removed by vacuum filtration,To the obtained filtrate, 240 ml of 10% sodium hydrogen carbonate was added,The liquidity of the aqueous layer was adjusted to pH 3.5,After adding 400 ml of ethyl acetate and vigorously stirring,The aqueous layer was separated,An organic layer containing olmesartan medoxomil was obtained (olmesartan medoxomil purity: 99.35%Dimer: 0.011%).200 ml of ethyl acetate was distilled off from the organic layer,After stirring at 20 to 30 C. for 1 hour,The precipitated solid was collected by filtration under reduced pressure as a wet body.The obtained wet body was dried at 40 C. for 14 hours,24 g of crystals of olmesartan medoxomil were obtained (yield: 86%, olmesartan medoxomil purity: 99.71%, dimer: 0.010%).

The chemical industry reduces the impact on the environment during synthesis, Triphenyl methyl olmesartan, , I believe this compound will play a more active role in future production and life.

Reference£º
Patent; Tokuyama Corporation; Mori, Hiroshi; Tanaka, Kenji; (12 pag.)JP6091339; (2017); B2;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

144690-92-6, A common heterocyclic compound, 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.”144690-92-6

A solution of MTT in an organic solvent and water (20%) was heated for 4-8 hrs at reflux. When the solvents were either acetonitrile (ACN), isopropyl alcohol (IPA) or t-butanol (t-BuOH), 1 volume of water was added, and the reaction was stirred until the amount of MTT was less than 2%. The mixture was evaporated to dryness. Ethyl acetate (EtOAc, 1 volume) was added to the residue and then evaporated again (twice). The resulting solid was dissolved in EtOAc (12 vol) and heated to reflux. The solution was cooled (2 C.) and stirred for 2 hrs. The product was filtered, washed (EtOAc, 1 vol), and dried on vacuum (45 C.). Table 1 shows the process details with different organic solvents: TABLE 1 Total solvent Time Solvent(s) Volume Temperature ( C.) (hrs) pH ACN:H2O 5:1 + 1 85 7 4.89-4.3 IPA:H2O 5:1 + 1 85 7 4.62-4.25t-BuOH:H2O 5:1 + 1 85 7 4.78-4.28n-propanol:H2O 5:1 reflux 2.5 4.3n-BuOH:H2O 5:1 110 2.5 4.412-BuOH:H2O 5:1 100 3 4.5iso-penthanol:H2O 5:1 100 3 5DMA:H2O 5:1 100 4 4.5DMF:H2O 5:1 100 4 4.5

With the complex challenges of chemical substances, we look forward to future research findings about Triphenyl methyl olmesartan

Reference£º
Patent; Hedvati, Lilach; Pilarsky, Gideon; Shenkar-Garcia, Natalia; US2006/148870; (2006); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

144690-92-6, A common heterocyclic compound, 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.”144690-92-6

A solution of MTT in an organic solvent and water (20%) was heated for 4-8 hrs at reflux. When the solvents were either acetonitrile (ACN), isopropyl alcohol (IPA) or t-butanol (t-BuOH), 1 volume of water was added, and the reaction was stirred until the amount of MTT was less than 2%. The mixture was evaporated to dryness. Ethyl acetate (EtOAc, 1 volume) was added to the residue and then evaporated again (twice). The resulting solid was dissolved in EtOAc (12 vol) and heated to reflux. The solution was cooled (2 C.) and stirred for 2 hrs. The product was filtered, washed (EtOAc, 1 vol), and dried on vacuum (45 C.). Table 1 shows the process details with different organic solvents: TABLE 1 Total solvent Time Solvent(s) Volume Temperature ( C.) (hrs) pH ACN:H2O 5:1 + 1 85 7 4.89-4.3 IPA:H2O 5:1 + 1 85 7 4.62-4.25t-BuOH:H2O 5:1 + 1 85 7 4.78-4.28n-propanol:H2O 5:1 reflux 2.5 4.3n-BuOH:H2O 5:1 110 2.5 4.412-BuOH:H2O 5:1 100 3 4.5iso-penthanol:H2O 5:1 100 3 5DMA:H2O 5:1 100 4 4.5DMF:H2O 5:1 100 4 4.5

The chemical industry reduces the impact on the environment during synthesis, Triphenyl methyl olmesartan, , I believe this compound will play a more active role in future production and life.

Reference£º
Patent; Hedvati, Lilach; Pilarsky, Gideon; Shenkar-Garcia, Natalia; US2006/148870; (2006); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

144690-92-6, A common heterocyclic compound, 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.”144690-92-6

Trityl olmesartan medoxomil (260 gm) as obtained in example 1 was dissolved in toluene (2600 ml) and then added concentrated hydrochloric acid (156 ml) for 1 hour minutes at room temperature. The reaction mass was maintained for 1 hour 30 minutes at room temperature and then added water (1000 ml). The reaction mass was stirred for 45 minutes at room temperature and the layers were separated. To the aqueous layer was added ethyl acetate (5000 ml) at room temperature. The reaction mass was cooled to 15 to 20 C. and pH of the reaction mass was adjusted to 4.5 to 5.5 with sodium carbonate (20%, 560 ml). The reaction mass was stirred for 20 minutes at 20 C. and the layers were separated. The organic layer was dried over sodium sulfate and ethyl acetate was distilled off completely under vacuum at below 45 C. to obtain a residual mass. To the residual mass was added ethyl acetate (400 ml) at 40 C. and then heated to 75 to 80 C. The contents were maintained for 30 minutes at 75 to 80 C. The reaction mass was cooled to room temperature and stirred for 1 hour. The reaction mass was further cooled to 10 to 15 C. and stirred for 1 hour 30 minutes, filtered. The solid obtained was dried at 40 to 45 C. for 4 hours to obtain 150 gm of olmesartan medoxomil. Olmesartan medoxomil: 98.6%; Olmesartan acid impurity: 0.32%; Trityl olmesartan medoxomil impurity: 0.35% Methyl olmesartan medoxomil impurity: 0.35%.

The chemical industry reduces the impact on the environment during synthesis, Triphenyl methyl olmesartan, , I believe this compound will play a more active role in future production and life.

Reference£º
Patent; HETERO RESEARCH FOUNDATION; Parthasaradhi Reddy, Bandi; Rathnakar Reddy, Kura; Muralidhara Reddy, Dasari; Raji Reddy, Rapolu; Ramakrishna Reddy, Matta; Vamsi Krishna, Bandi; US2013/190506; (2013); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

144690-92-6, A common heterocyclic compound, 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.”144690-92-6

To the three-necked flask were added with 38 ml of ethyl acetate, 45 g of 6.4% dilute hydrochloric acid, 25 g of trityl olmesartan medoxomil was added with stirring. Stir in water bath, control the temperature 15 to 20 C, stirring about 4 hours, TLC plate detection point of raw material disappeared,That is, it is judged that the deprotection reaction is completed.Cooled to room temperature, 115 ml * 5 toluene was added to wash, the aqueous layer was added with 135 ml of acetone, potassium bicarbonate aqueous solution adjusted P=4.0, control temperature 15 ¡À 5 C Stir for 2 hours, Filtered and dried to give 16.0 g of olmesartan medoxomil in a yield of 90.2%. HPLC analysis: purity 98.75%, impurity a (olmesartan acid) 0.71%, individual impurities less than 0.10%

144690-92-6 is used more and more widely, we look forward to future research findings about Triphenyl methyl olmesartan

Reference£º
Patent; Zhejiang Huahai Pharmaceutical Co., Ltd,; Huang, Xiangliang; Zhang, LI; Hua, yuanyuan; Wu, Yong De; (7 pag.)CN102584804; (2016); B;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

Triphenyl methyl olmesartan, A common heterocyclic compound, 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.”144690-92-6

A solution of MTT in an organic solvent and water (20%) was heated for 4-8 hrs at reflux. When the solvents were either acetonitrile (ACN), isopropyl alcohol (IPA) or t-butanol (t-BuOH), 1 volume of water was added, and the reaction was stirred until the amount of MTT was less than 2%. The mixture was evaporated to dryness. Ethyl acetate (EtOAc, 1 volume) was added to the residue and then evaporated again (twice). The resulting solid was dissolved in EtOAc (12 vol) and heated to reflux. The solution was cooled (2 C.) and stirred for 2 hrs. The product was filtered, washed (EtOAc, 1 vol), and dried on vacuum (45 C.). Table 1 shows the process details with different organic solvents: TABLE 1 Total solvent Time Solvent(s) Volume Temperature ( C.) (hrs) pH ACN:H2O 5:1 + 1 85 7 4.89-4.3 IPA:H2O 5:1 + 1 85 7 4.62-4.25t-BuOH:H2O 5:1 + 1 85 7 4.78-4.28n-propanol:H2O 5:1 reflux 2.5 4.3n-BuOH:H2O 5:1 110 2.5 4.412-BuOH:H2O 5:1 100 3 4.5iso-penthanol:H2O 5:1 100 3 5DMA:H2O 5:1 100 4 4.5DMF:H2O 5:1 100 4 4.5

The chemical industry reduces the impact on the environment during synthesis, Triphenyl methyl olmesartan, , I believe this compound will play a more active role in future production and life.

Reference£º
Patent; Hedvati, Lilach; Pilarsky, Gideon; Shenkar-Garcia, Natalia; US2006/148870; (2006); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem