Month: December 2020

80841-78-7, The molecularity is the number of molecules that collide during that step in the mechanism. If only a single reactant molecule in an elementary reaction, that step is designated as unimolecular; if there are two reactant molecules, it is bimolecular.80841-78-7. A new synthetic method of this compound is introduced below.

130 ml of N,N-dimethylacetamide, 14.0 g (20 mmol) of ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-((2′-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-1H-imidazole-5-carboxylate and 2.2 g (16 mmol) of KOH were charged into reaction vessel at room temperature under inert atmosphere. The mixture was stirred at room temperature for 2 h, and then the sample of reaction mixture was analysed (HPLC; starting material 0.2 %, hydrolysed starting material 98.11 %). Then 3.0 g (2.2 mmol) of potassium carbonate powder and 1.4 g (8.4 mmol) of potassium iodide were added. The reaction 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 97.22 %, 4-(2-hydroxypropan-2-yl)-2-propyl-1-((2′-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-1H-imidazole-5-carboxylate 0.09 %). The mixture was cooled to 10 to 20 C 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, the cake washed with cold acetonitrile and dried at 40 to 50C. Yield: 17.0 g (94%) HPLC: 99.72 % of the product, all impurities are under 0.1%. IR: 3408, 1818, 1805, 1741, 1681, 1529, 1147, 1003, 699 XRD:

A chemical reaction often occurs in steps, although it may not always be obvious to an observer.

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

One of the major reasons is to use measurements of the macroscopic properties of a system, the rate of change in the concentration of reactants or products with time, to discover the sequence of events that occur at the molecular level. 37830-90-3, introduce a new downstream synthesis route. 37830-90-3

(1) 2.08 g of 4,5-dimethyl-1,3-dioxol-2-one was dissolved in 24 mL of benzene, to which 3.25 g of N-bromosuccinimide and 86 mg of 2,2′-azobis(isobutyronitrile) were added at room temperature, and this mixture was stirred for 30 minutes while heating it under reflux. The reaction mixture was cooled to room temperature, and consequently, a solution of 4-bromomethyl-5-methyl-1,3-dioxol-2-one in benzene was obtained.(2) 3.00 g of methyl 3-(5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-{[3-(methoxymethoxy)-1,2-benzisoxazol-6-yl]methoxy}phenyl) propanoate was dissolved in 15 mL of methanol and 15 mL of tetrahydrofuran, to which a solution of 1.08 g of potassium hydroxide in 4.5 mL of water was added, and this mixture was stirred for one hour at room temperature, and then the solvent was distilled out under reduced pressure. The resultant residue was dissolved in 40 mL of N,N-dimethylformamide, to which 3.60 g of potassium carbonate was added. Then, the benzene solution prepared in (1) was added thereto, and was stirred for one hour at room temperature. The reaction mixture was poured into a mixture of ethyl acetate and water, and adjusted to pH 7 with 6M hydrochloric acid, and then the organic phase was separated therefrom. After the resultant organic phase was washed with water and a saturated sodium chloride solution successively, the washed phase was dried over anhydrous sodium sulfate, and the solvent was distilled out under reduced pressure. The resultant residue was purified by silica gel column chromatography [eluent; toluene:ethyl acetate=5:1] to yield 1.58 g of (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 3-(5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-{[3-(methoxymethoxy)-1,2-benzisoxazol-6-yl]methoxy}phenyl) propanoate as yellow oil. NMR(400MHz,CDCl3) delta value: 1.5-2.0(8H,m), 2.16(3H,s), 2.75(2H,t,J=7.6Hz), 3.10(2H,t,J=7.6Hz), 3.65(3H,s), 4.5-5.0(3H,m), 5.33(2H,s), 5.57(2H,s), 6.37(1H,dd,J=8.8,2.4Hz), 6.47(1H,d,J=2.4Hz), 6.95(1H,d,J=8.4Hz), 7.35(1H,dd,J=8.4,1.2Hz), 7.4-7.6(4H,m), 7.72(1H,d,J=8.0Hz), 12.67(1H,s).

There are, however, a few established termolecular elementary reactions. The reaction of nitric oxide with oxygen appears to involve termolecular steps.

Reference£º
Patent; TOYAMA CHEMICAL CO., LTD.; Hirono, Shuichi; Shiozawa, Shunichi; EP1445249; (2004); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

80841-78-7, The molecularity is the number of molecules that collide during that step in the mechanism. If only a single reactant molecule in an elementary reaction, that step is designated as unimolecular; if there are two reactant molecules, it is bimolecular.80841-78-7. A new synthetic method of this compound is introduced below.

Example 5; Preparation of trityl olmesartan medoxomilTo dimethyl sulphoxide (800 ml), sodium hydroxide powder (50 gms) was added under nitrogen atmosphere and stirred at 20-250C for 10 minutes. To this, 4-( 1 -hydroxy- 1- methylethyl)-2-propyl-imidazole-5-ethyl carboxylate (100 gms) was added at 20-250C. 5- (4′-bromomethyl-biphenyl)-2-yl-1 -trityl tetrazole (270 gms) was added slowly at 20-250C, and the reaction mass was stirred at 20-250C for 12 hours. Further 10% sodium hydroxide solution (100 ml) was added to the reaction mass at 20-250C. The temperature of the reaction mass was raised to 40-450C, the contents stirred at 40-450C for 2 hours and 5- methyl-2-oxo-1 ,3-dioxane-4-yl)methyl chloride (160 gms) was added slowly at 45-5O0C over a period of 45 minutes. The contents were stirred at 45-5O0C for 2 hours. The reaction mass was then cooled to 0-50C, stirred for 1 hour at 0-50C, filtered and slurried in water (1.0 It) at 40-450C for 1 hour, filtered at 4O0C and dried at 4O0C. To the dried material, ethyl acetate (2.5 It) was added, heated to 50-550C for complete dissolution, ethyl acetate was distilled off to 1.0 It stage under vacuum at 45-5O0C. The contents were cooled to 0-50C, stirred at 0-50C for 3 hours, filtered, washed with chilled methanol (100 ml) and dried under vacuum at 40-450C to give 250 gms of the title compound. Purity by HPLC : > 99%

This molecular description is the mechanism of the reaction; it describes how individual atoms, ions, or molecules interact to form particular products. The stepwise changes are collectively called the reaction mechanism.

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

80841-78-7, The molecularity is the number of molecules that collide during that step in the mechanism. If only a single reactant molecule in an elementary reaction, that step is designated as unimolecular; if there are two reactant molecules, it is bimolecular.80841-78-7. A new synthetic method of this compound is introduced below.

To a solution of the compound of Formula IV (5.0 g) in toluene (40 mL), dimethylacetamide (10 mL) is added, followed by addition of sodium hydroxide (1.2 g) and N,N-diisopropylamine (3.7 g) at 25-35C. The mixture is stirred at 40- 45C for 4 hours. 5-Methyl-2-oxo-(1 ,3-dioxolene-4-yl)methyl chloride (1.5 g) and tetrabutylammonium bromide (0.5 g) are added at 40-450C. The mixture is stirred at 60-70C for 8 hours. The mass is cooled to 25-35C, water (50 mL) 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 (25 mL). The organic layers are combined and washed with water (25 mL). The solvent is distilled under reduced pressure. Methanol (25 mL) is added to the residue. The mixture is cooled to 0-50C and stirred at that temperature for 45 minutes. The formed solid is filtered, washed with methanol (10 mL) and dried for 45 minutes under vacuum (yield 3.0 g).

A chemical reaction often occurs in steps, although it may not always be obvious to an observer.

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

144690-92-6, The molecularity is the number of molecules that collide during that step in the mechanism. If only a single reactant molecule in an elementary reaction, that step is designated as unimolecular; if there are two reactant molecules, it is bimolecular.144690-92-6. A new synthetic method of this compound is introduced below.

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%).

A chemical reaction often occurs in steps, although it may not always be obvious to an observer.

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

The molecularity is the number of molecules that collide during that step in the mechanism. If only a single reactant molecule in an elementary reaction, that step is designated as unimolecular; if there are two reactant molecules, it is bimolecular.37830-90-3. A new synthetic method of this compound is introduced below., 37830-90-3

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).

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 4,5-Dimethyl-1,3-dioxol-2-one reaction routes.

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

Rate laws may be derived directly from the chemical equations for elementary reactions. This is not the case, however, for ordinary chemical reactions.80841-78-7, molecula formula is 4-(Chloromethyl)-5-methyl-1,3-dioxol-2-one, below Introduce a new synthetic route., 80841-78-7

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]+.

Elementary reactions that involve the simultaneous collision of more than three molecules are highly improbable and have never been observed experimentally.

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

144690-92-6, The molecularity is the number of molecules that collide during that step in the mechanism. If only a single reactant molecule in an elementary reaction, that step is designated as unimolecular; if there are two reactant molecules, it is bimolecular.144690-92-6. A new synthetic method of this compound is introduced below.

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%.

This molecular description is the mechanism of the reaction; it describes how individual atoms, ions, or molecules interact to form particular products. The stepwise changes are collectively called the reaction mechanism.

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, The molecularity is the number of molecules that collide during that step in the mechanism. If only a single reactant molecule in an elementary reaction, that step is designated as unimolecular; if there are two reactant molecules, it is bimolecular.144690-92-6. A new synthetic method of this compound is introduced below.

Trityl olmesartan medoxomil (8 g, 10 mmol) is dissolved in THF (50 ml) and 48 % aqueous hydrobromic acid (3.5 ml, 30 mmol) is added. The mixture is stirred for 1 hour at room temperature and then 1 hour at 0 C. The precipitate is filtered, washed with cold THF (20 ml) and dried overnight in vacuum at room temperature to give 5.7 g of olmesartan medoxomil hydrobromide Form B (98.6 % area)

There are, however, a few established termolecular elementary reactions. The reaction of nitric oxide with oxygen appears to involve termolecular steps.

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

One of the major reasons is to use measurements of the macroscopic properties of a system, the rate of change in the concentration of reactants or products with time, to discover the sequence of events that occur at the molecular level. 144690-92-6, introduce a new downstream synthesis 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

There are, however, a few established termolecular elementary reactions. The reaction of nitric oxide with oxygen appears to involve termolecular steps.

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