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Trityl olmesartan medoxomil (250 g, 310 mmol) (97.3 % area) is dissolved in THF (1560 ml) and 48 % aqueous hydrobromic acid (70.6 ml, 625 mmol) is added slowly. The mixture is stirred for at 25 C. After 1 hour the precipitate forms. The mixture is stirred for 1 additional hour at 25 C, then cooled to -5 C and stirred for 1.5 hours at -5 C. The precipitate is filtered. 940 ml of THF is added to the precipitate and the mixture is stirred for 1 h at 25 C and then 1 hour at -5 C. Then precipitate is filtered off and washed with cold THF (150 ml). It is then dissolved in a mixture of water (875 ml) and acetone (440 ml). To a clear solution 5 % aqueous solution of NaHCO3 is added to raise pH to 5.15. The mixture is stirred for 1 hour at room temperature and 1 hour at 0 C. The precipitate is filtered, washed with water and then recrystallized from a mixture of acetonitrile (280 ml) and water (70 ml) to give 124.5 g of olmesartan medoxomil (99.68 % area)

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

Brief introduction of 144690-92-6

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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).

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

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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%).

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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

Extracurricular laboratory: Synthetic route of 144690-92-6

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In heterogeneous catalysis, the catalyst is in a different phase from the reactants. 144690-92-6, At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 144690-92-6, name is C48H44N6O6. In an article£¬Which mentioned a new discovery about 144690-92-6

The reaction flask was charged with 400 g of compound VII (0.50 mol) and 70% aqueous acetic acid solution of 3200 ml, Reaction was carried out at 50 C for 2 hours. After the completion of the reaction, the solvent was concentrated and concentrated, and ammonia was added to the residue.PH = 7, extracted with 1400 ml of ethyl acetate, the ethyl acetate layer was washed with water, and finally with anhydrous sodium sulfateDried; filtered, the filtrate was concentrated to dryness and the residue was recrystallized from ethanol to give the compound I pure product 256.1G, yield: 91.79%.

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Reference£º
Patent; Hunan Ouya biological Co. Ltd.; Lin, kaizhao; (19 pag.)CN103304550; (2016); B;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

New downstream synthetic route of 144690-92-6

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144690-92-6,Children learn through play, and they learn more than adults might expect. Science experiments are a great way to spark their curiosity, get their minds active, and encourage them to do something that doesn¡¯t involve a screen. C48H44N6O6,introducing its new discovery.

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

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

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In heterogeneous catalysis, the catalyst is in a different phase from the reactants. 144690-92-6, At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 144690-92-6, name is C48H44N6O6. In an article£¬Which mentioned a new discovery about 144690-92-6

Example 7; Preparation of olmesartan medoxomilTo 75 % aqueous acetic acid (1000 ml) was slowly added trityl olmesartan medoxomil (110 gms)[prepared as described in example 5] at 25-30C. The contents were stirred at 600C 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 (500 ml), neutralized with a 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 the acetone (250 ml) to give 55 gms of the title compound. Chromatogrphic purity – > 99%

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

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144690-92-6,Children learn through play, and they learn more than adults might expect. Science experiments are a great way to spark their curiosity, get their minds active, and encourage them to do something that doesn¡¯t involve a screen. C48H44N6O6,introducing its new discovery.

61(b) (5-Methyl-2-oxo-1,3-dioxolen-4yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}methylimidazole-5-carboxylate A mixture of 1.4 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] and 48 ml of 75% v/v aqueous acetic acid was stirred at 60 C. for 1 hour, after which it was concentrated by evaporation under reduced pressure. The residue was dissolved in toluene, and the resulting solution was concentrated by distillation under reduced pressure; this was repeated a further time in order to remove the remaining water and acetic acid. The residue thus obtained was purified by column chromatography through silica gel using 1:9 and 1:4 by volume mixtures of methanol and methylene chloride as the eluent, to give 0.73 g of the title compound, melting at 170-172 C. Nuclear Magnetic Resonance Spectrum (CDCl3), delta ppm: 0.93 (3H, triplet, J=7.5 Hz); 1.63 (6H, singlet); 1.6-1.8 (2H, multiplet); 2.19 (3H, singlet); 2.70 (2H, triplet, J=7.5 Hz); 5.00 (2H, singlet); 5.45 (2H, singlet); 6.83 (2H, doublet, J=8 Hz); 7.10 (2H, doublet, J=8 Hz); 7.42-7.63 (3H, multiplet); 7.83 (1H, doublet of doublets, J=1 & 7.5 Hz).

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

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144690-92-6,is a common compound. C48H44N6O6In an article, once mentioned the new application about 144690-92-6.

(4) the C48 H44 N6 O6 AMST – 6, acetone, water, sulfuric acid added to the reactor, the temperature rising to 30 C reaction 2.5 hours, adding water, 30 C continue to reaction 1.5 hours or more, when the raw material to achwhich isve the requirement of lowering the temperature to 5 C stirring 1 or more hours, filtering the triphenyl methanol, the filter cake is washed with water; mother liquor up to 50 C, add sodium bicarbonate, stirring 1 hour, filtration products, the filter cake is washed with water, 50 C decompression drying 12 hours or more to constant weight, to obtain omay sha tanzhi thick; said C48 H44 N6 O6 AMST – 6, acetone, water, sulfuric acid and sodium bicarbonate and the mass ratio of 700:1400:: 2101.4: 194.7: 373.5; (5) the crude product of olmesartan medoxomil and acetone is added to the reaction in the bottle, heat to reflux to totally dissolve, filter press, distilling off acetone, lowering the temperature to -10 C crystallization, filtration, acetone washing, 50 C drying productC29 H30 N6 O6 Olmesartan medoxomil, the crude with olmesartan medoxomil mass ratio of olmesartan medoxomil 448.4: 6500;

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Reference£º
Patent; Jiangxi Yong Tong Technology Co., Ltd.; Liu Zhongchun; (10 pag.)CN107311989; (2017); A;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

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144690-92-6,Children learn through play, and they learn more than adults might expect. Science experiments are a great way to spark their curiosity, get their minds active, and encourage them to do something that doesn¡¯t involve a screen. C48H44N6O6,introducing its new discovery.

Example 1-6 (0333) (0334) A mixture of TOLM (0.6 g, 0.75 mmol), sulfuric acid (0.08 g, 0.82 mmol) and 1:1 water-containing acetic acid (2.6 mL, 4.3 vol) was stirred at 25 C. for 1 hr. The reaction mixture was filtered, and the obtained solid was washed with 1:1 water-containing acetic acid (6.0 mL, 10 vol). The filtrates were combined and adjusted to pH 4-5 by adding 25% aqueous sodium carbonate solution. The mixture was partitioned by adding methylene chloride (6.0 mL, 10 vol). The aqueous layer was extracted with methylene chloride (3¡Á5 mL). The organic layer was washed with water (2¡Á5 mL) and saturated brine (5 mL), and concentrated under reduced pressure. The concentrated residue was purified by silica gel column chromatography (5-6% methanol/methylene chloride) and recrystallized from acetonitrile to give OLM (0.45 g, yield 100%). (0335) melting point: 174.5 C.-175.2 C.; (0336) IR (KBr): numax=2969, 1831, 1706, 1475, 1226, 1134, 760 cm-1; (0337) 1H NMR (DMSO-d6): delta=7.70-7.63 (m, 2H), 7.59-7.52 (m, 2H). (0338) 7.04 (d, J=8 Hz, 2H), 6.85 (d, J=8.4 Hz, 2H), 5.42 (s, 2H), 5.21 (s, 1H), 5.05 (s, 2H), 2.60 (t, J=7.6 Hz, 2H), 2.07 (s, 3H), 1.60-1.55 (m, 2H), 1.47 (s, 6H), 0.87 (t, J=7.2 Hz, 3H); (0339) Mass: 559 [M+H]+.

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Reference£º
Patent; API CORPORATION; Seki, Masahiko; US2015/239854; (2015); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

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A 250 round bottom flask was loaded with MTT (10 g), acetone/water (2/2 vol.), and 3 eq of H2SO4. The mixture was stirred at 40 C., and after 2-4 hrs, triphenyl carbinol (TPC) was precipitated by the addition of water and filtrated out. NaHCO3 was added to the filtrate and the mixture was cooled to room temperature and stirred for 1 hr. Crude olmesartan medoxomil was obtained as white crystals (90% yield).

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Reference£º
Patent; Hedvati, Lilach; Pilarsky, Gideon; US2006/149078; (2006); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem