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Some tips on Triphenyl methyl olmesartan

144690-92-6, 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.,144690-92-6 ,Triphenyl methyl olmesartan, other downstream synthetic routes, hurry up and to see

Name is Triphenyl methyl olmesartan, as a common heterocyclic compound, it belongs to Dioxole compound, and cas is 144690-92-6, its synthesis route is as follows.

Example 5; Olmesartan medoxomil (V); Water (10 g) was added to a solution of the starting substance (III; 20 g) in acetonitrile (50 ml), and the mixture was heated to a mild boil for 14 h. Acetonitrile was evaporated, and, after dissolving in acetone (150 ml), the mixture was filtered through alumina and concentrated. After crystallization from the mixture tetrahydrofuran / ethyl acetate H g (78 %) of the product with an HPLC purity of 97.0 % was obtained. Recrystallization from methanol and water gave 1O g of the product with an HPLC purity of 99.3 %; m.p. 175- 177 0C.; Example 6; Olmesartan medoxomil (V); Water (10 g) was added to a solution of the starting substance (III; 10 g) in acetonitrile (50 ml), and the mixture was heated to a mild boil for 14 h. Acetonitrile was evaporated, and, after dissolving in acetone (150 ml), the mixture was filtered through silica gel and concentrated. After crystallization from acetonitrile, 4 g (57 %) of the product was obtained. After recrystallization from the mixture methyl tert-butyl ether / ethyl acetate, 3.4 g of the product with an HPLC purity of 99.4 % was obtained; m.p. 175-177 C.

Reference£º
Patent; ZENTIVA, A.S.; WO2007/48361; (2007); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

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The chemical industry reduces the impact on the environment during synthesis,144690-92-6,Triphenyl methyl olmesartan,I believe this compound will play a more active role in future production and life.

144690-92-6, 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. Triphenyl methyl olmesartan, cas is 144690-92-6,the Dioxole compound, it is a common compound, a new synthetic route is introduced below.

To 2000mL four-neck flask equipped with two stirring bladesof diameter 15 cm, tritylolmesartan medoxomil100 g, acetic acid450 ml, water 150mLwere added, & stirred for 2 hours at 40 C and deprotection reaction was carried out. Thereaction solution was then cooled to 20 C, stirred for 1 hour at 20 C, and precipitated triphenyl methanol wasremoved by filtrationunder reduced pressure, and to the resulting filtrate, 10% sodium bicarbonate 500ml, ethyl acetate1000ml were added and after vigorousstirrind, the aqueous layer was separated, to obtain an organic layercontaining olmesartanmedoxomil. ethylacetate 400ml was evaporated from the organic layer, and stirred for 1 hour at20 ~ 30 , and the precipitated solid was done filtration under reduced pressure and fractionated aswet product. The resulting wet product was dried for 14 hours at 40 , the crude olmesartan medoxomil wasobtained 60g(residual ethyl acetate content: 5420ppm, the residual amount of acetic acid:490ppm, purity: 99.37%). In 100mL three-necked flask equipped with two stirringblades of diameter 2.5 cm, crude olmesartan medoxomil 5g obtained in ProductionExample 1, acetone 15 ml, ethyl acetate 15 mL, water 3g were added and heatedto 60 C, to obtain a solution of olmesartan medoxomil (solution adjustingstep). then cooled to 30 C, and after adding seed crystals of olmesartanmedoxomil, it was stirred for 15 hours at 28 C (crystallization step: it wasconfirmed that there is no change in the amount of crystals even if it isretained for more time.) .

Reference£º
Patent; TOKUYAMA CORPORATION; MORI, HIROYUKI; TANAKA, KENJI; (13 pag.)JP2016/65007; (2016); A;,
1,3-Benzodioxole – Wikipedia
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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 Triphenyl methyl olmesartan, 144690-92-6

78(b) (5-Methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}methylimidazole-5-carboxylate 75 ml of water were added to a suspension of 29.3 g of (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(trityltetrazol-5-yl)phenyl]phenyl}methylimidazole-5-carboxylate [prepared as described in step (a) above] in 225 ml of acetic acid, and the resulting mixture was stirred at 60 C. for 1.5 hours. At the end of this time, 75 ml of water were added to the mixture, which was then cooled. Precipitated trityl alcohol was removed by filtration, and the filtrate was concentrated by evaporation under reduced pressure. Toluene was added to the residue, and the mixture was again concentrated by evaporation under reduced pressure, to remove the remaining water and acetic acid. The residue was crystallized in ethyl acetate, to give 16.6 g of the title compound as crystals, melting at 177-180 C. (with decomposition). The Nuclear Magnetic Resonance Spectrum of this compound was identical with that of the compound obtained as described in Example 61(b).

Reference£º
Patent; Sankyo Company, Limited; US5616599; (1997); A;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

Application of 2,3-Dihydrobenzo[b][1,4]dioxine-2-carboxylic acid

As a common heterocyclic compound, it belongs to Dioxole compound, name is Triphenyl methyl olmesartan, and cas is 144690-92-6, its synthesis route is as follows.

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

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

New learning discoveries about 144690-92-6

It is a common heterocyclic compound, the Dioxole compound, Triphenyl methyl olmesartan, cas is 144690-92-6 its synthesis route is as follows.

Trityl olmesartan medoxomil (8 g, 10 mmol) is added to a mixture of acetone (35 ml) and water (10 ml). To the resulting suspension 37 % aqueous hydrochloric acid (2.5 ml, 30 mmol) is added. The mixture is then stirred at room temperature for 4 h. Water (130 ml) is added and the mixture is stirred for additional 30 minutes. The precipitated triphenylmethanol is filtered off. The filtrate is concentrated in vacuum at 40 C to 100 ml, and then stirred vigorously for 1 h at room temperature and then additional 30 minutes at 0 C. The precipitate is filtered to give 4.7 g of olmesartan medoxomil hydrochloride Form A (98.3 % area)

Reference£º
Patent; LEK Pharmaceuticals d.d.; EP2022790; (2009); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

The important role of 144690-92-6

As a common heterocyclic compound, it belongs to Dioxole compound, name is Triphenyl methyl olmesartan, and cas is 144690-92-6, its synthesis route is as follows.

Example 1; Preparation of olmesartan medoxomilTo dimethyl acetamide (300 ml) was added 4-(1-hydroxy-1-methylethyl)-2-propyl imidazol- 5-carboxylic acid ethyl ester (50 gms) and powdered sodium hydroxide (26 gms). To this, 4-[2-(trityltetrazol-5-yl)phenyl]benzyl bromide (135 gms) was charged at 45-500C. The contents were stirred for 5 hours at 45-500C. Diisopropylethyl amine (100 ml) was charged to the reaction mass at 40-450C. A solution of 5-methyl-2-oxo-1 , 3-dioxane-4-yl)methyl chloride (80 gms) diluted with dimethyl acetamide (160 ml) was slowly added to the reaction mass at 40-450C over a period of 1 hour. The contents were heated to 60-650C and maintained for 4 hours. The reaction mass was then cooled to 30-350C and neutralized with concentrated hydrochloride acid. The reaction mass was filtered to remove inorganic impurities, charcoalized using charcoal (10 gms) andstirred for 30 minutes at 40-450C. The reaction mass was filtered over hyflo. The clear filtrate was acidified with hydrochloric acid (100 ml) slowly at 25-30C. The contents were stirred at 60C for 1 hour. The reaction mass was chilled to 0-5C and filtered to remove tritanol. The reaction mass was concentrated under reduced pressure. The residue was quenched with water (500ml), neutralized with base and extracted in dichloromethane (500 ml). The clear dichloromethane extract was then concentrated under reduced pressure and stripped off with acetone. The residue thus obtained was isolated from acetone (250 ml) to give 55 gms of the title compound. Chromatographic purity- > 99%; Example 2Preparation of olmesartan medoxomilTo dimethyl acetamide (600 ml) was added 4-(1-hydroxy-1-methylethyl)-2-propyl imidazol- 5-carboxylic acid ethyl ester (100 gms) and powdered potassium hydroxide (50 gms). To this was charged 4-[2-(trityltetrazol-5-yl)phenyl]benzyl bromide (270 gms) at 45-50C. The contents were stirred for 5 hours at 45-50C. Diisopropylethyl amine (200 ml) was charged to the reaction mass at 40-450C. To this was slowly added a solution of 5-methyl-2-oxo- 1 ,3-dioxane-4-yl)methyl chloride (160 gms) diluted with dimethyl acetamide (320 ml) at 40- 45C over a period of 1 hour. The contents were heated to 60-650C and maintained for 4 hours. The reaction mass was then cooled to 30-350C and was neutralized with concentrated hydrochloride acid. The reaction mass was filtered to remove inorganic impurities. The reaction mass was charcoalized using charcoal (20 gms) and was stirred for 30 minutes at 40-450C. The reaction mass was filtered over hyflo. The clear filtrate was acidified with hydrochloric acid (200 ml) slowly at 25-300C. The contents were stirred at 60C for 1 hour. The reaction mass was chilled to 0-50C and was filtered to remove tritanol. The reaction mass was concentrated under reduced pressure. The residue was quenched with water (1000 ml), neutralized with base and extracted in dichloromethane (1000 ml). The clear dichloromethane extract was then concentrated under reduced pressure, stripped off with acetone. The residue thus obtained was isolated from the acetone (500 ml) to give 110 gms of the title compound. Chromatogrphic purity- > 99%; Example 3Preparation of olmesartan medoxomilTo dimethyl acetamide (800 ml) was added 4-(1-hydroxy-1-methylethyl)-2-propyl imidazol- 5-carboxylic acid ethyl ester (100 gms) and powdered potassium carbonate (200 gms). To this was charged 4-[2-(trityltetrazol-5-yl)phenyl]benzyl bromide (300 gms) at 45-50C. The contents were stirred for 8-10 hours at 45-50C. The insolubles were filtered. The contents were cooled to 5-100C. Potassium tertiary butoxide (100 gms) was charged at a temperature below 45C. The reaction was maintained at 40-450C for 3 hrs. To this was slowly added 5-methyl-2-oxo-1 ,3-dioxane-4-yl) methyl chloride at 40-450C over a period of 1 hour. The contents were heated to 60-650C and maintained for 4 hours. The reaction mass was then cooled to 30-350C and was neutralized with concentrated hydrochloride acid. The reaction mass was filtered to remove inorganics. The reaction mass was charcoalized using charcoal (10 gms) and was stirred for 30 minutes at 40-450C. The reaction mass was filtered over hyflo. The clear filtrate was acidified with hydrochloric acid (100 ml) slowly at 25-30C. The contents were stirred at 60C for 1 hour. The reaction mass was chilled to 0-5C and was filtered to remove tritanol. The reaction mass was concentrated under reduced pressure. The residue was quenched with water (500 ml), neutralized with base and extracted in dichloromethane (500 ml).The clear dichloromethane extract was then concentrated under reduced pressure, stripped off with acetone. The residue thus obtained was isolated from the acetone (250 ml) to give 55 gms of the title compound. Chromatogrphic purity- > 99%

Reference£º
Patent; CIPLA LIMITED; CURTIS, Philip, Anthony; WO2008/43996; (2008); A2;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

Application of 2,3-Dihydro-1,4-benzodioxine-6-carboxylic acid

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%

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

Introduction of a new synthetic route about 144690-92-6

As a common heterocyclic compound, it belongs to Dioxole compound, name is Triphenyl methyl olmesartan, and cas is 144690-92-6, its synthesis route is as follows.

Example 1 – formation of olmesartan medoxomil hydrobromide Form A Trityl olmesartan medoxomil (8 g, 10 mmol) is added to a mixture of acetone (35 ml) and water (10 ml). To the resulting suspension 48 % aqueous hydrobromic acid (3.5 ml, 30 mmol) is added. The mixture is then stirred at room temperature for 2 h. Water (130 ml) is added and the mixture is stirred for additional 30 minutes. The precipitated triphenylmethanol is filtered off. The filtrate is concentrated in vacuum at 40 C to 100 ml, and then stirred vigorously for 1 h at room temperature and then additional 30 minutes at 0 C. The precipitate is filtered to give 4.7 g of olmesartan medoxomil hydrobromide Form A (97.6 % area); Example 9 – formation of olmesartan medoxomil Trityl olmesartan medoxomil (18 g, 22.5 mmol) (95.5 % area) is added to a mixture of acetone (68 ml) and water (22 ml). To the resulting suspension 48 % aqueous hydrobromic acid (8.5 ml, 72 mmol) is added. The mixture is then stirred at room temperature for 2 h. Water (180 ml) is added and the mixture is stirred for additional 15 minutes. The precipitated triphenylmethanol is filtered off. The filtrate is concentrated in vacuo at 40 C to 200 ml and then stirred vigorously for 20 minutes at room temperature and then additional 40 minutes at 0 C. The precipitate is filtered and dried overnight in vacuum at 25 C to give 12.9 g of olmesartan medoxomil hydrobromide Form A. This was added to THF (150 ml) and the mixture is stirred vigorously for 30 minutes at room temperature and 1 hour at 0 C. The precipitate is filtered and washed with 25 ml of cold THF to give olmesartan medoxomil hydrobromide Form B, which is then dissolved in a mixture of water (100 ml) and acetone (50 ml). To a clear solution saturated aqueous NaHCO3 is added to raise pH to 5.6. The mixture is stirred for 1 hour at room temperature and 2 hours at 0 C. The precipitate is filtered, washed with water and then recrystallised from acetonitrile (87 ml) to give 8.3 g of olmesartan medoxomil (99.74 % area)

Reference£º
Patent; LEK Pharmaceuticals d.d.; EP2022790; (2009); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

The important role of Triphenyl methyl olmesartan

As a common heterocyclic compound, it belongs to Dioxole compound, name is Triphenyl methyl olmesartan, and cas is 144690-92-6, its synthesis route is as follows.

A 250 round bottom flask was charged with MTT (10 g), acetone/water (2/2 vol.), and 3 eq of H2SO4. The combination was stirred at room temperature for about 4-6 hrs. Triphenyl carbinol (TPC) was precipitated by adding water and filtered out. NaHC03 was added to the filtrate, and the mixture was cooled to 5C and stirred for 1 hr. Crude olmesartan medoxomil was obtained as white crystals (90% yield).Example 2: Preparation of crude olmesartan medoxomil AIL reactor, equipped with mechanical stirrer and thermometer, was charged with MTT (70 g), acetone (140 ml), water (140 ml), and H2S04 (19.47 g). The reactor was heated to 40C for 2.5 hrs (at EOR, MTT is LT 1%). Water (140 ml) was added at 40C, and the reaction was stirred for 1.5 hrs or until MTT is LT 0.1%. After cooling to 15C and stirring for 1 hr, the TPC was filtered and washed with water (70 ml).NaHC03 was added in portions to the filtrate at room temperature. The reaction mixture was stirred for 1 hr, then filtrated, and the cake was washed with water (140 ml). The solid was dried at 45C in a vacuum oven overnight to obtain crude OLM-Mod (98 % yield).

Reference£º
Patent; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2006/29056; (2006); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

Analyzing the synthesis route of 144690-92-6

Take 40g of compound 5, Add 80mL of methanol, 330 mL of ethyl acetate, Warmed to 45 , After 8 hours of reaction, Add 860mL water, Insoluble matter was removed by filtration, The filtrate was concentrated, In oily liquid, Acetonitrile, Stirred under a solid precipitation, filter, Washed with ethanol, 23.2 g of white solid was obtained, The yield was 83.1% The HPLC purity was 99.2%.

Reference£º
Patent; Disha Pharmaceutical Group Co., Ltd.; Zhang Zhaoxing; Zhang Hongqiang; Qin Litai; Li Wei; Li Zongwen; Xia Haijian; (6 pag.)CN103012382; (2016); B;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem