Category: 144690-92-6

Triphenyl methyl olmesartan, A common heterocyclic compound, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.”144690-92-6

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.) .

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

Reference£º
Patent; TOKUYAMA CORPORATION; MORI, HIROYUKI; TANAKA, KENJI; (13 pag.)JP2016/65007; (2016); A;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

144690-92-6, A common heterocyclic compound, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.”144690-92-6

Example 8; To a solution of (5-Methyl-2-oxo-1,3-dioxolen-4-yl)methyl-4-(1-hydroxy-1-methyl ethyl)-2-propyl-1-{4-[2-(trityltetrazol-5-yl)phenyl]phenyl}methylimidazole-5-carboxylate (5.0 g; 6.25 mmol) and toluene (20 ml) at 15-20 C. is added hydrochloric acid (30 ml). Reaction mass is stirred at 15-20 C. for about 15 minutes to 4 hours. The reaction is monitored by TLC. After completion of reaction layers are separated. Aqueous layer is washed with toluene (10 ml). Adjusted the pH of the aqueous layer to 5-6 using aqueous potassium carbonate solution (200 ml) and the compound is extracted using ethyl acetate (60 ml). Combined ethyl acetate layers are washed with brine. Finally crude product (3.1 g; 89.8%) is isolated by evaporation of solvent under reduced pressure.Purity: 99.5%

With the complex challenges of chemical substances, we look forward to future research findings about Triphenyl methyl olmesartan,belong Dioxole compound

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

Triphenyl methyl olmesartan, A common heterocyclic compound, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.”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).

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

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

144690-92-6, A common heterocyclic compound, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.”144690-92-6

A mixture of trityl olmesartan medoxomil (4.0 g), methanol (20 mL), and water (10 mL) is stirred at 25-35C for 15 minutes. Aqueous HCI (1 mL) is added drop-wise at 25-35C. The mixture is cooled to 0-50C. Water (30 mL) is added and the mixture is further stirred at 0-5C for 1 hour. The insoluble material is removed by filtration and the pH of the filtrate is adjusted to about 3-4 by adding 10% aqueous NaHCOs at 25-35C. The mixture is extracted with dichloromethane (3chi40 ml_). The organic layers are combined and washed with water (40 ml_). The solvent is distilled under reduced pressure below 400C. Ethyl acetate (10 ml_) is added to the residue and the mixture is heated to 50-600C and stirred for 1 hour. The mixture is cooled to 25-35C. The formed solid is filtered, washed with ethyl acetate (5 ml_), and dried under vacuum at 60-700C (yield 2.0 g).

With the complex challenges of chemical substances, we look forward to future research findings about Triphenyl methyl olmesartan

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, A common heterocyclic compound, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.”144690-92-6

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]+.

With the complex challenges of chemical substances, we look forward to future research findings about Triphenyl methyl olmesartan,belong Dioxole compound

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

144690-92-6, A common heterocyclic compound, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.”144690-92-6

One hundred ml of methanol was added to 10 g of (5-methyl-2-oxo-l,3-dioxol- 4-yl) methyl 4-(2-hydroxypropan-2-yl)-2-propyl-l-((2′-(l-trityl-lH-tetrazol-5-yl) biphenyl-4-yl) methyl)-lH-imidazole-5-carboxylate (Pharmacostech). Then to the reaction mixture was added 10 g of resin pre-treated with hydrochloric acid of pH 2-3 (TRILUE SCR-IO gel type), followed by refluxing for 6 hours. The solid components were filtered out from the reaction mixture and washed with 100 ml of methanol. The solid substance obtained by vacuum distillation of the filter-in solution was dissolved into a small quantity of acetone, and n-hexane was added to the acetone solution to obtain 6.58 g (yield rate: 94%) of the standard compound represent by Formula 9: 1H NMR (300 MHz, DMSO), delta 7.50-7.69 (m, 4H), 7.03 (d, 2H, J=8.0 Hz), 6.85 (d, 2H, >8.0 Hz), 5.41 (s, 2H), 5.22 (s, IH), 5.05 (s, 2H), 2.50 (s, 2H), 2.07 (s, 3H).

With the synthetic route has been constantly updated, we look forward to future research findings about Triphenyl methyl olmesartan,belong Dioxole compound

Reference£º
Patent; PHARMACOSTECH CO., LTD.; KIM, Jae Won; CHA, Young Gwan; RYU, Hyung Chul; KIM, Sun Joo; WO2010/67913; (2010); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

144690-92-6, A common heterocyclic compound, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.”144690-92-6

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.

With the complex challenges of chemical substances, we look forward to future research findings about 144690-92-6,belong Dioxole compound

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

144690-92-6, A common heterocyclic compound, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.”144690-92-6

Example 2 Olmesartan medoxomil of formula I20 g of the starting compound of formula III were stirred up in 75 ml of acetic acid and after stirring for 10 minutes 30 ml of water were added dropwise during 5 minutes. Then, the suspension was put in a 50C bath and stirred for 4 hours. Then 16 ml of water were added dropwise in 5 minutes, the mixture was taken out of the bath and after 5 minutes it was put in a cooling bath with the temperature of 10C. After 20 minutes the separated insoluble fraction, containing the side product trityl alcohol, was aspirated and washed with a mixture of 4 ml of AcOH + 2 ml of water. 40 ml of acetone and then 70 ml of water were added to the filtrate at 30C, the separated product was aspirated and 1 1.5 g (82 %) of the product were obtained., 144690-92-6

As the rapid development of chemical substances, we look forward to future research findings about 144690-92-6

Reference£º
Patent; ZENTIVA, K. S.; STACH, Jan; JARRAH, Kamal; KRULIS, Radim; RADL, Stanislav; CERNY, Josef; WO2012/55380; (2012); A1;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem

Triphenyl methyl olmesartan, A common heterocyclic compound, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.”144690-92-6

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)

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

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

144690-92-6, A common heterocyclic compound, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.”144690-92-6

Into a 1000 mL four-necked flask equipped with a two-piece stirring blade having a diameter of 10 cm,50 g of trityl olmesartan medoxomil, 225 ml of acetic acid and 75 ml of water were added and stirred at 40 C. for 2 hours to carry out deprotection reaction.Subsequently, the reaction solution was cooled to 20 C. and stirred at 20 C. for 1 hour, and the precipitated triphenylmethanol was removed by vacuum filtration,To the obtained filtrate were added 250 ml of 10% sodium hydrogen carbonate and 500 ml of ethyl acetate, followed by vigorous stirring, and the aqueous layer was separated to obtain an organic layer containing olmesartan medoxomil.200 ml of ethyl acetate was distilled off from the organic layer, and the mixture was stirred 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 to obtain 30 g of crystals of olmesartan medexomil (purity: 99.54%)., 144690-92-6

As the rapid development of chemical substances, we look forward to future research findings about 144690-92-6

Reference£º
Patent; TOKUYAMA CORPORATION; MORI, HIROYUKI; TANAKA, KENJI; (11 pag.)JP2015/74608; (2015); A;,
1,3-Benzodioxole – Wikipedia
Dioxole | C3H4O2 – PubChem