Category: 651780-27-7

A common heterocyclic compound, 651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, 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. 651780-27-7

651780-27-7, 10% Palladium on carbon (1.5g) and triethylamine (7.5 g, 82.4 mmol) were added to a solution of ethyl 6-bromobenzisoxazole-3-carboxylate (20g, 0. 081mol) in ethanol (300ml) at 0 C under an atmosphere of nitrogen. The nitrogen atmosphere was removed by evacuation and replaced with hydrogen gas, and the reaction mixture was maintained for 1 hour. The hydrogen atmosphere was removed by evacuation and replaced with nitrogen gas, and the palladium removed by filtration through Celite. The filter cake was washed with ethanol (3 x 50 mL) and the filtrates were concentrated. The residue was dissolved in dichloromethane (200 mL) and the solution was washed with water (4 x 50 mL), dried (sodium sulfate) and evaporated to provide 13.0 g of the product as a yellow solid (96%). The ester was saponified using sodium hydroxide to provide the acid. The acid was coupled with the bicyclobase according to procedure A. Literature reference: Angell, R. M.; Baldwin, I. R.; Bamborough, P.; Deboeck, N. M.; Longstaff, T.; Swanson, S. W004010995A1 The following acid was prepared using this method: 1,2-Benzisoxazole-3-carboxylic acid.

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate,651780-27-7,its application will become more common.

Reference£º
Patent; MEMORY PHARMACEUTICALS CORPORATION; WO2005/63767; (2005); A2;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

A common heterocyclic compound, 651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, 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. 651780-27-7

10% Palladium on carbon (1.5 g) and triethylamine (7.5 g, 82.4 mmol) were added to a solution of ethyl 6-bromobenzisoxazole-3-carboxylate (20 g, 0.081 mol) in ethanol (300ml) at 0 C. under an atmosphere of nitrogen. The nitrogen atmosphere was removed by evacuation and replaced with hydrogen gas, and the reaction mixture was maintained for 1 hour. The hydrogen atmosphere was removed by evacuation and replaced with nitrogen gas, and the palladium removed by filtration through Celite. The filter cake was washed with ethanol (3¡Á50 mL) and the filtrates were concentrated. The residue was dissolved in dichloromethane (200 mL) and the solution was washed with water (4¡Á50 mL), dried (sodium sulfate) and evaporated to provide 13.0 g of the product as a yellow solid (96%). The ester was saponified using sodium hydroxide to provide the acid. The acid was coupled with the bicyclobase according to procedure A., 651780-27-7

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate,651780-27-7,its application will become more common.

Reference£º
Patent; Xie, Wenge; Herbert, Brian; Ma, Jianguo; Nguyen, Truc Minh; Schumacher, Richard; Gauss, Carla Maria; Tehim, Ashok; US2005/250808; (2005); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

A common heterocyclic compound, 651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, 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. 651780-27-7

20a) Ethyl 6-(4-hydroxyphenyl)-l,2-benzisoxazole-3-carboxylateEthyl 6-bromo-l,2-benzisoxazole-3-carboxylate (0.34 g, 1.26 mmol), (4- hydroxyphenyl)boronic acid (0.21, 1.51 mmol), tetrakis(triphenylphosphine)palladium (0) (0.06 g, 0.05 mmol) and 2 M sodium carbonate (5 mL) in 1 ,2-dimethoxyethane (6 mL) were stirred at 80 0C for 1 hour. The reaction mixture was diluted with water, followed by ethyl acetate. The layers were separated and the ethyl acetate layer was washed with brine, dried over magnesium sulfate, filtered, and concentrated to afford the crude material. The crude material was purified using hexanes: ethyl acetate (0 to 40% ethyl acetate) to afford a mixture of desired product, plus the free acid of the desired product, 6-(4-hydroxyphenyl)-l,2- benzisoxazole-3-carboxylic acid. All the fractions were combined and concentrated.

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate,its application will become more common.

Reference£º
Patent; SMITHKLINE BEECHAM CORPORATION; WO2008/157270; (2008); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

A common heterocyclic compound, 651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, 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. 651780-27-7

To a mixture of ethyl 6-bromobenzisoxazole-3-carboxylate (2.0 g, 7.4 mmol) and t- butyl 5-cyanoanthranilate (1.62 g, 7.4 mmol) in toluene (27 [ML)] is added NaH (1.5 g of a 60% mineral oil dispersion, 3.8 mmol) under N2. The reaction mixture is stirred overnight at rt. This mixture is diluted with aq 1 N [HCI,] extracted with EtOAc (0.2 L). The EtOAc solution is dried and concentrated to give Preparation Pb as a solid : 1H NMR (300 MHz, CDC13) [8] 12.8 (1H), 9.05 [(1H),] 8.38 (1H), 8.18 (1H), 7.92 (1H), 7.82 (1H), 7.61 [(1H),] [1.] 69 [(9H).]

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate,its application will become more common.

Reference£º
Patent; PHARMACIA & UPJOHN COMPANY; WO2004/18428; (2004); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

651780-27-7 A common heterocyclic compound, 651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, 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.

Diethyl malonate (12.6 g, 79 mmol) was added to a suspension of sodium hydride (3.16 g, 132 mmol) in dimethylsulfoxide (60 ml) over 30 min. The temperature of the reaction rose to 60 C and the mixture clarified. 1,4-Dibromo-2-nitrobenzene (10 g, 36.0 mmol) was added and the solution was maintained for 2 h at 100 C. The reaction mixture was allowed to cool to rt and was poured into ice (300g-400g). The precipitated solids were isolated by filtration and dried to provide 11.0 g of the product (89%). The ester (11.0 g, 32.0 mmol) was diluted with a 2 N solution of sodium hydroxide (32 mL, 63 mmol) and the reaction mixture was maintained at room temperature for 16 h. The aqueous layer was extracted with dichloromethane (20 mL) and was acidified. The precipitated solids were isolated by filtration and dried to provide 7.00 g of the acid (89%). Sulfuric acid (1 mL) was added to a solution of the acid (7.00 g, 27.0 mmol) in ethanol (60 ml). The reaction mixture was warmed to reflux, maintained for 2 h, and was concentrated under reduce pressure. The residue was partitioned between ethyl acetate (250 mL) and saturated sodium carbonate (50 mL) and the organic layer was washed with saturated sodium carbonate (50 mL) and brine (50 mL). The organic layer was dried (sodium sulfate) and concentrated to provide 8.00 g (98%) of the ester as a liquid. Under N2 atmosphere, sodium ethylate was formed with sodium (33.5 g, 1.46 mol) in ethanol (1.0 L). Isoamylnitrite (225 mL) was added to a solution of the ester (420 g, 1.46 mol) in ethanol (3 L) in a 10 L three-necked round bottom flask and the mixture was warmed to 60 C. A solution of sodium ethoxide, prepared from sodium metal (33.5 g, 1.46 mmol) in ethanol (1 L) was added dropwise and the reaction mixture was maintained for 2 h. The reaction mixture was allowed to cool to rt and was neutralized with 2 N hydrochloric acid. The reaction mixture was extracted with ethyl acetate (4 x 2L) and the combined organic layers were washed with water (2 x 1 L) and brine (2 x 1 L) and dried (sodium sulfate). The residue was purified by chromatography (1/1 to 0/1 hexane/ethyl acetate) to provide 110 g of the product ( 28%). 10% Palladium on carbon (1.5g) and triethylamine (7.5 g, 82.4 mmol) were added to a solution of ethyl 6-bromobenzisoxazole-3-carboxylate (20g, 0.081mol) in ethanol (300ml) at 0 C under an atmosphere of nitrogen. The nitrogen atmosphere was removed by evacuation and replaced with hydrogen gas, and the reaction mixture was maintained for 1 hour. The hydrogen atmosphere was removed by evacuation and replaced with nitrogen gas, and the palladium removed’by filtration through Celite. The filter cake was washed with ethanol (3 x 50 mL) and the filtrates were concentrated. The residue was- dissolved in dichloromethane (200 mL) and the solution was washed with water (4 x 50 mL), dried (sodium sulfate) and evaporated to provide 13.0 g of the product as a yellow solid (96%). The ester was saponified using sodium hydroxide to provide the acid. The acid was coupled with 1,4-diazabicyclo[3.2.2]nonane according to procedure A.

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate,its application will become more common.

Reference£º
Patent; MEMORY PHARMACEUTICALS CORPORATION; WO2005/111038; (2005); A2;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

A common heterocyclic compound, 651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, 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. 651780-27-7

A mixture of ethyl 6-bromobenzoisoxazole-3-carboxylate (550 mg, 1.39 mmol), o- tolylboronic acid (377 mg, 1.5 [EQ),] Pd (PPh3) 4 (171 mg, 0.08 [EQ),] toluene (10 mL), ethanol (1.5 mL), and 1 M [NA2C03] (1.5 [ML)] is stirred at reflux for 3.5 h. The reaction mixture is diluted with [CHUCK] (0.1 L) and [H2O] (0.1 mL). The [CHZC12] solution is dried [(NA2S04),] filtered, and evaporated. The residue is purified by silica chromatography (heptane/EtOAc) to give Preparation [PA.’H] NMR (300 MHz, CDC) 8 8.14 (1H), 7.61 (2H), 7.42 (1H), 7.35-7. 2 (1H), 4.59 (2H), 2.28 (3H), 1.51 (3H).

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate,its application will become more common.

Reference£º
Patent; PHARMACIA & UPJOHN COMPANY; WO2004/18428; (2004); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

651780-27-7 A common heterocyclic compound, 651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, 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.

Step 3 6-(4-Hvdroxy-2-methyl-phenyl’)-benzordlisoxazole-3-carboxylic acid ethyl esterA solution of 3-methyl-4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-phenol (0.624 g, 2.67 mmol) and 6-bromo-benzo[d]isoxazole-3-carboxylic acid ethyl ester (0.360 g, 1.33 mmol) in 1,4-dioxane (20 mL) is added to a flask. The flask is evacuated and re-filled with N2 3 times. To this solution, Pd2(dba)3 (0.010 g), tricyclohexyl phosphine (10 mg), and aqueous K3PO4 (1.5 mL, 1.30 M) are added. The resulting mixture is heated to 50 C for 2 hours under N2. The reaction mixture is cooled to room temperature and filtered through a pad of diatomaceous earth. The filtrate is concentrated under reduced pressure. The residue is purified via silica gel chromatography eluting with 25% ethyl acetate in hexanes to give the title compound (0.366 g, 93%). ES/MS m/e 298.0 (M+l); 296.0 (M-I).

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate,its application will become more common.

Reference£º
Patent; ELI LILLY AND COMPANY; WO2007/92751; (2007); A2;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

A common heterocyclic compound, 651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, 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. 651780-27-7

10% Palladium on carbon (1.5g) and triethylamine (7.5 g, 82.4 mmol) were added to a solution of ethyl 6-bromobenzisoxazole-3-carboxylate (20g, 0. 081mol) in ethanol (300ml) at 0 C under an atmosphere of nitrogen. The nitrogen atmosphere was removed by evacuation and replaced with hydrogen gas, and the reaction mixture was maintained for 1 hour. The hydrogen atmosphere was removed by evacuation and replaced with nitrogen gas, and the palladium removed by filtration through Celite. The filter cake was washed with ethanol (3 x 50 mL) and the filtrates were concentrated. The residue was dissolved in dichloromethane (200 mL) and the solution was washed with water (4 x 50 mL), dried (sodium sulfate) and evaporated to provide 13.0 g of the product as a yellow solid (96%). The ester was saponified using sodium hydroxide to provide the acid. The acid was coupled with the bicyclobase according to procedure A. Literature reference: Angell, R. M.; Baldwin, I. R.; Bamborough, P.; Deboeck, N. M.; Longstaff, T.; Swanson, S. W004010995A1 The following acid was prepared using this method: 1,2-Benzisoxazole-3-carboxylic acid., 651780-27-7

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate,651780-27-7,its application will become more common.

Reference£º
Patent; MEMORY PHARMACEUTICALS CORPORATION; WO2005/63767; (2005); A2;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

A common heterocyclic compound, 651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, 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. 651780-27-7

Diethyl malonate (12.6 g, 79 mmol) was added to a suspension of sodium hydride (3.16 g, 132 mmol) in dimethylsulfoxide (60 ml) over 30 min. The temperature of the reaction rose to 60 C and the mixture clarified. 1,4-Dibromo-2-nitrobenzene (10 g, 36.0 mmol) was added and the solution was maintained for 2 h at 100 C. The reaction mixture was allowed to cool to rt and was poured into ice (300g-400g). The precipitated solids were isolated by filtration and dried to provide 11.0 g of the product (89%). The ester (11.0 g, 32.0 mmol) was diluted with a 2 N solution of sodium hydroxide (32 mL, 63 mmol) and the reaction mixture was maintained at room temperature for 16 h. The aqueous layer was extracted with dichloromethane (20 mL) and was acidified. The precipitated solids were isolated by filtration and dried to provide 7.00 g of the acid (89%). Sulfuric acid (1 mL) was added to a solution of the acid (7.00 g, 27.0 mmol) in ethanol (60 ml). The reaction mixture was warmed to reflux, maintained for 2 h, and was concentrated under reduce pressure. The residue was partitioned between ethyl acetate (250 mL) and saturated sodium carbonate (50 mL) and the organic layer was washed with saturated sodium carbonate (50 mL) and brine (50 mL). The organic layer was dried (sodium sulfate) and concentrated to provide 8.00 g (98%) of the ester as a liquid. Under N2 atmosphere, sodium ethylate was formed with sodium (33.5 g, 1.46 mol) in ethanol (1.0 L). Isoamylnitrite (225 mL) was added to a solution of the ester (420 g, 1.46 mol) in ethanol (3 L) in a 10 L three-necked round bottom flask and the mixture was warmed to 60 C. A solution of sodium ethoxide, prepared from sodium metal (33.5 g, 1.46 mmol) in ethanol (1 L) was added dropwise and the reaction mixture was maintained for 2 h. The reaction mixture was allowed to cool to rt and was neutralized with 2 N hydrochloric acid. The reaction mixture was extracted with ethyl acetate (4 x 2L) and the combined organic layers were washed with water (2 x 1 L) and brine (2 x 1 L) and dried (sodium sulfate). The residue was purified by chromatography (1/1 to 0/1 hexane/ethyl acetate) to provide 110 g of the product ( 28%). 10% Palladium on carbon (1.5g) and triethylamine (7.5 g, 82.4 mmol) were added to a solution of ethyl 6-bromobenzisoxazole-3-carboxylate (20g, 0.081mol) in ethanol (300ml) at 0 C under an atmosphere of nitrogen. The nitrogen atmosphere was removed by evacuation and replaced with hydrogen gas, and the reaction mixture was maintained for 1 hour. The hydrogen atmosphere was removed by evacuation and replaced with nitrogen gas, and the palladium removed’by filtration through Celite. The filter cake was washed with ethanol (3 x 50 mL) and the filtrates were concentrated. The residue was- dissolved in dichloromethane (200 mL) and the solution was washed with water (4 x 50 mL), dried (sodium sulfate) and evaporated to provide 13.0 g of the product as a yellow solid (96%). The ester was saponified using sodium hydroxide to provide the acid. The acid was coupled with 1,4-diazabicyclo[3.2.2]nonane according to procedure A.

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate,its application will become more common.

Reference£º
Patent; MEMORY PHARMACEUTICALS CORPORATION; WO2005/111038; (2005); A2;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics

651780-27-7 A common heterocyclic compound, 651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, 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.

651780-27-7, Toluene (40 mL) was added to a flask containing ethyl [6-BROM-1,] 2-benzisoxazole-3-carboxylate (3.15 g, 11.7 mmol), tetrakis (triphenylphosphine) palladium [(0)] (835 mg, 0.723 mmol, Strem), cesium carbonate (4.12 g, 12.6 mmol, Aldrich), and 2- (trifluoromethyl) phenylboronic acid (2. [38] g, 12.5 mmol, Aldrich) under argon. This mixture was heated in a 100 C oil bath for 35 hours. The mixture was diluted with EtOAc (250 mL) and washed with 4: 1 water: brine (250 [ML)] followed by brine (250 mL). The organics were filtered through a [1″PLUG] of silica gel and evaporated. Product was split in two, adsorbed onto silica gel, and purified on Biotage Flash 40 M+ silica cartridges using 20% EtOAc in heptane. Yield was 2.08 g of orange solid. [‘H] NMR (400 MHz, DMSO-d6) [5] ppm 1.42 (t, [J=7.] 15 Hz, 3 H) 4.51 (q, [J=7.] 05 Hz, 2 H) 7.52 (d, J=7. 46 Hz, [1] H) 7.51 (d, [J=8.] 09 Hz, 1 H) 7.71 (t, J=7. 57 Hz, [1] H) 7.79 (t, [J=7.] 36 Hz, 1 H) 7.91 (d, [J=7.] 67 Hz, [1] [H)] 7.93 (s, 1 H) 8.14 (d, J=8. 09 Hz, 1 H).

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate,its application will become more common.

Reference£º
Patent; PHARMACIA & UPJOHN COMPANY; WO2004/18428; (2004); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics