Continuously updated synthesis method about 4,5-Dimethyl-1,3-dioxol-2-one

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Example 26 Preparation of 5-methyl-4-hydroxymethyl-2-oxo-1,3-dioxolene A mixture of 4,5-dimethyl-2-oxo-1,3-dioxolene (1 mmol) and selenium dioxide (2.5 mmol) in dioxane was heated at reflux for 1 h. Evaporation, extraction and chromatography gave 5-methyl-4-hydroxymethyl-2-oxo-1,3-dioxolene as a yellow oil. TLC: Rf=0.5, 5percent MeOH-dichloromethane.

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Reference£º
Patent; Metabasis Therapeutics, Inc.; US6054587; (2000); A;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

Downstream synthetic route of 4,5-Dimethyl-1,3-dioxol-2-one

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37830-90-3,In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a article,4,5-Dimethyl-1,3-dioxol-2-one,introducing its new discovery.

To a solution of 16 grams 4,5-dimethyl-1, 3-dioxol-2-one in CC14 (250 mE) was added N135 (23.4 g,131.5 mmol) and AII3N (1.3 g, 7.88 mmol), then the reaction mixture was heated to 80¡ã C. and stirred for 2 hrs. Monitored the starting material gone by TLC. The mixture was filtered and the filtrate was washed with water and brine, the organic phase was dried over Na2504 and concentrated to give crude product as a yellow oil which was used directly next step (25.3 g, yield 93percent).

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Reference£º
Patent; KULING THERAPEUTICS; DING, Qiang; Wang, Xiaohu; (55 pag.)US2017/298090; (2017); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

Downstream synthetic route of 4-(Chloromethyl)-5-methyl-1,3-dioxol-2-one

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Example 7; Preparation of Trityl Olmesartan Medoxomil4-(1-Hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(trityltetrazol-5-yl)phenyl]phenyl}methylimidazole-5-carboxylic acid dehydrate (100 g) was suspended in acetone (1 L) & heated to reflux; the solution obtained was added to suspension of potassium carbonate (15 g), potassium iodide (6 g) & 4-chloromethyl-5-methyl-1,3-dioxol-2-one (35 g) in acetone (500 mL) at reflux temperature. Reaction mass was refluxed for 2-6 hrs. After competition of reaction, the reaction mass was filtered & the acetone was distilled from combined mother liquor. The residue obtained was dissolved in toluene (1 L) toluene layer was washed with brine (3¡Á250 mL). Toluene was removed under reduced pressure & residue thus obtained was recrystallized from methanol to give trityl OlmesartanMedoxomil (100 g).HPLC purity=99.5%

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Reference£º
Patent; Ramanjaneyulu, Gorantla Seeta; Mohan, Bandari; Ray, Purna Chandra; Sethi, Madhuresh Kumar; Rawat, Vijendra Singh; Krishna, Yerramalla Raja; Lakshminarayana, Vemula; Srinivas, Mamidi; US2009/281327; (2009); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

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Example 1-5 (0330) (0331) A mixture of BIC (0.6 g, 0.83 mmol), potassium iodide (0.069 g, 0.41 mmol), OXC (0.245 g, 1.65 mmol) and methyl ethyl ketone (9.0 mL, 15 vol) was stirred at 50 C. for 20 hr. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure, and the obtained concentrated residue was purified by silica gel column chromatography (20-22% ethyl acetate/hexane) to give TOLM (650 mg, yield 84.4%). (0332) Mass: 801 [M+H]+, 824 [M+Na]+.

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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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37830-90-3,In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a article,4,5-Dimethyl-1,3-dioxol-2-one,introducing its new discovery.

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

The origin of a common compound about 4-(Chloromethyl)-5-methyl-1,3-dioxol-2-one

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Toluene (180 L) is placed into a reactor and water (3.17 L) is added, followed by addition of ethyl-4-(1 -hydroxy-1 -methylethyl)-2-propylimidazole-5- carboxylate (18.0 Kg). The mass is stirred for about 10 minutes, heated to about 45C, and potassium carbonate (25.85 Kg) is added. The temperature of the mass is raised to about 65C and maintained for about 45 minutes. N-(triphenylmethyl)- 5-[4′-(bromomethyl)biphenyl-2-yl]tetrazole (48.9 Kg) and tetrabutylammonium bromide (4.82 Kg) are added at the same temperature and the mixture is stirred at 60-700C for 10 hours. Reaction completion is verified using thin layerchromatography (TLC). After the reaction is complete, the mass is washed with water (3*120 L) at about 500C. The mass is cooled to about 25C and toluene (468 L) and potassium tertiary-butoxide (12.6 Kg) is added, then the mass is maintained at the same temperature for about 1 hour. Water (0.85 L) is added and the mass is maintained at the same temperature for about 2 hours. Reaction completion is verified using TLC, then 5-methyl-2-oxo-(1 ,3-dioxolene-4-yl)methyl chloride (20 Kg), tetrabutylammonium bromide (4.82 Kg), and sodium carbonate (3.96 Kg) are added at 40-450C. The mass is stirred at about 55C for about 11 hours. After the reaction is complete, the mass is cooled to about 20C, water (540 L) is added and the pH is adjusted to about 6-7 by adding 10% aqueous HCI. The layers are separated. The aqueous layer is extracted with toluene (240 L). The organic layers are combined and washed with water (270 L). The solvent is distilled under reduced pressure. Acetone (189 L) is added to the residue and the mixture is heated to about 45C to produce a solution, then the solution is cooled to about 300C and maintained for about 20 minutes, followed by cooling to about 2C and maintaining for about 3 hours. The formed solid is filtered, washed with acetone (54 L), and dried for about 4 hours. The material obtained is re- crystallized from acetonitrile to yield 34.0 Kg of the title compound.

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Reference£º
Patent; DR. REDDY’S LABORATORIES LTD.; DR. REDDY’S LABORATORIES, INC.; KOLLA, Naveen Kumar; MANNE, Nagaraju; NAREDLA, Anitha; SHINDE, Sachin Gulabrao; WO2011/14611; (2011); A2;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

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In 130 ml of N,N-dimethyl acetamide, 14.5 g (20 mmol) of potassium 4-(2-hydroxypropan-2-yl)-2-propyl-1-((2′-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-1H-imidazole-5-carboxylate, 3.0 g (2.2 mmol) of potassium carbonate powder and 1.4 g (8.4 mmol) of potassium iodide were added. The mixture was cooled to 0 C and 5.0 g (33 mmol) of 4-(chloromethyl)-5-methyl-1,3-dioxol-2-one was added at 0 to 5C. After the addition, the reaction mixture was warmed to 40-45 C within one hour, then the mixture was stirred at this temperature for 2h. The sample of reaction mixture was analysed (HPLC; tritylolmesartan medoxomil, 97.44%, 4-(2-hydroxypropan-2-yl)-2-propyl-1-((2′-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-1H-imidazole-5-carboxylate 0.06 %). The mixture was cooled to 10 to 20C and then 250 ml of ethyl acetate was added. The mixture was cooled again to 5-10 C and then 200 ml of 10% NaCl was added slowly. The temperature should not be higher than 25 C during the addition. The phases were mixed separated and organic phase was washed with 100 ml of 10% NaCl (2*) and dried over anhydrous sodium sulphate. After the filtration filtrate was evaporated under reduced pressure at temperature under 45C to oily residue. To the residue 30 ml of acetonitrile was added at temperature not more than 45C. The mixture was stirred at this temperature for 10 minutes then was cooled to 20 to 25C and stirred at this temperature for 0.5 h and after that 3h at 0 to 5C. The suspension was filtered, washed with cold acetonitrile and dried at 40 to 50C. Yield: 17.0 g (91%) HPLC: 99.64 % of the product, all other impurities under 0.1%. IR: 3408, 1818, 1805, 1741, 1681, 1529, 1148, 1002, 699

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

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Example 2; 36.0 g (50.3 mmol) ethyl 4-(l -hydroxy- 1-methy lethyl)-2-propy 1-1- {4-[2-(trityltetrazol-5-y I)- 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 00C and solution of 15.4 g (70.4 mmol) 4-chloromethyl-5-methyl-2-oxo-l,3- dioxolene in 39 ml of dimethylacetamide were slowly added. The mixture was slowly heated to 500C and stirred at this temperature for 2 h. After esterification was completed, the mixture was cooled to 10 0C and poured into a mixture of 625 ml of ethyl acetate and 625 ml of 10 % NaCl, and stirred at 25 0C for 15 min. The phases were separated and organic phase was washed 2chi with 500 ml of 10 % NaCl, dried over Na2SO4 and filtered. The filtrate was concentrated up to 14 (approximately 270 g) at reduced pressure.To the resulting solution, 80 ml of ethanol and 8.3 ml (100 mmol) of cone. HCl were added EPO 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 0C and stirred for Ih, 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; WO2007/17135; (2007); A2;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

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1L glass reaction flask was added with 600ml of acetone, 114.8g of intermediate 1 was added with stirring, then 12.8g of sodium hydroxide was added, the temperature was raised to 50-60 C, and the reaction was incubated for 5 hours, and the reaction was monitored by HPLC. To 20-30 C, add 2.8g potassium iodide, 36.0g 4-chloromethyl-5-methyl-1,3-dioxol-2-one, and increase the temperature to 50-60 C after the addition After 1 hour of heat preservation reaction, the temperature was lowered to 20-30 C, filtered, and the filter cake was rinsed with 115 ml of acetone, and the filtrate was combined. The filtrate was concentrated under reduced pressure at 40-50 C until no obvious solvent flowed out, and 320 ml of acetonitrile was added to cool down. The mixture was decanted to 20-30 C for 1 hour, filtered, and the filter cake was rinsed with 320 ml of acetonitrile. The filter cake was blast dried at 40-50 C for 12 hours to obtain a white solid 110.0 g (intermediate 2). The rate was 85.8%, HPLC: 99.2%.

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Reference£º
Patent; Jiashi (Hunan) Pharmaceutical Technology Co., Ltd.; Dai Yongzhi; Liu Hu; Zhu Laifa; Cai Jian; (8 pag.)CN108341804; (2018); A;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

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To BIC (110 g, 1 eq) was added acetone (385 mL, 3.5 vol) at 25C – 30C, and the mixture was dissolved by stirring for 5 min. Sodium carbonate (20.85 g, 1.3 eq) and potassium iodide (0.25 g, 0.01) were added, and the mixture was stirred for 10 min. A solution of 4-chloromethyl-5-methyl-2-oxo-1,3-dioxolene (31.456 g, 1.4 eq) in acetone (165 mL, 1.5 vol) was added thereto. The reaction mixture was heated to 45C – 50C, and stirred at the same temperature for 12 hr. Using TLC (thin layer chromatography) (TLC eluent: 10% methanol/methylene chloride, detection method: UV), complete disappearance of BIC was confirmed. The reaction mixture was cooled to 25C – 30C. Then, the solvent contained in the reaction mixture was evaporated under reduced pressure at 40C – 45C. To the obtained residue were added 10% brine (550 mL, 5 vol) and toluene (550 mL, 5 vol). Furthermore, the mixture was adjusted to pH 7 – 8 by adding 5% hydrochloric acid (33 mL), stirred for 10 min, left standing for 5 min and partitioned. The aqueous layer was extracted with toluene (2×330 mL, 2×3 vol). The extracts were combined with the organic layer, 10% brine (550 mL, 5 vol) was added, and the mixture was stirred for 5 min, left standing for 45 min, partitioned, and concentrated under reduced pressure at 40C – 45C to give TOLM (110 g, 90%). [0306] To the obtained TOLM was added acetone (110 mL, 1 vol), and the mixture was stirred at 25C – 30C for 30 min. n-Heptane (440 mL, 4 vol) was added, and the mixture was cooled to 5C – 10C and stirred at 5C – 10C for 30 min, whereby precipitation of a solid was confirmed. The solid (80 g, 66%) was collected by filtration, and blast dried. To the obtained solid was added isopropyl alcohol (400 mL, 5 vol), and the mixture was heated to 50C – 55C and stirred at 50C – 55C for 1 hr. Then, the mixture was cooled to 25C – 30C, and stirred at 25C – 30C for 1 hr. The resulting solid was filtered and suction-filtered for 10 min to give TOLM (76 g, 62%).

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Reference£º
Patent; API Corporation; SEKI, Masahiko; EP2891650; (2015); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem