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80841-78-7,Chemistry can be defined as the study of matter and the changes it undergoes. You¡¯ll sometimes hear it called the central science because it is the connection between physics and all the other sciences, starting with biology.4-(Chloromethyl)-5-methyl-1,3-dioxol-2-one,introducing its new discovery.

Example 3; Preparation 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%

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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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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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Example 236.0 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 0 C. 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 50 C. 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 2¡Á 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 24-26 C. for 3 h. 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 1 h, filtered off and washed with 20 ml of fresh ethyl acetate. The yield of the product (I) was 21 g (75%).

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Reference£º
Patent; KRKA; US2009/131680; (2009); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

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37830-90-3, To a solution of 4,5-dimethyl-1,3-dioxolene-2-one (TCI, 10 g, 88 mmol) and N- bromosuccinimide (Fluka, 15.69 g, 88 mmol) in carbon tetrachloride (250 mL) was added benzoyl peroxide (Acros, 500 mg, 2.1 mmol). The reaction mixture was then refluxed for 2.5 h after which time the volatiles were evaporated under vacuum. The resulting residue was triturated with some carbon tetrachloride, filtered and the solid cake was washed with carbon tetrachloride. The filtrate volatiles were removed under vacuum and the yellow oily residue was distilled under vacuum (2-5 torr) to give 4-bromomethyl-5-methyl-1,3-dioxolene-2-one 903 (8.35 g, b.p. 94-98 ¡ãC, 49percent) as a pale yellow oil. 1H NMR (CDCI3) 8 4.21 (s, 2H), 2.17 (s, 3H).

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Reference£º
Patent; RIGEL PHARMACEUTICALS, INC.; WO2005/97760; (2005); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

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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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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)

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

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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%.

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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

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A mixture of 4,5-dimethyl-1,3-dioxol-2-one (1.0 g, 8.8 mmol), benzoylperoxide (60 mg, 0.25 mmol) and N-bromosuccinimide (1.6 g, 9.0 mmol) in carbon tetrachloride (10 mL) was heated at reflux for 2 h. The solid was removed from the reaction mixture by filtration. The mother liquid was washed with sat. NaHCO3 and brine, dried over MgSO4 and concentrated. The crude product, 4-(bromomethyl)-5-methyl-1,3-dioxol-2-one, was obtained as a yellow oil (1.7 g) and was used without further purification in the next step.

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Reference£º
Patent; Martinsson, Jessica; Faernegardh, Katarina; Joensson, Mattias; Ringom, Rune; US2015/25068; (2015); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

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10L autoclave, 520g (0.75mol) Compound 5, DMF3kg, potassium carbonate and 215.3g (1.6mol), stirred at room temperature 1.5-2.5h added to the system after 63.0g (0.38mol) of potassium iodide was added dropwise while – Chloromethyl -5-methyl-1,3-dioxol-2-one 40.0g (0.94mol). Dropping was completed, the reaction at room temperature after 3-4h TLC or HPLC in control, raw reaction was complete. To the system was added ethyl acetate and 3L 3L water and 200g of sodium chloride, stirring separated and the aqueous layer was washed with 3X1L ethyl acetate, the combined organic layers, the organic layer was dried, filtered and the solvent was evaporated cooling is added 0-10 , methanol was added 1600g beating 30min, filtered, then the filter cake was slurried at room temperature in acetonitrile 1600g 30min, filtered to afford intermediate 6 about 553.8g,

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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

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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%).

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