Any one of these steps may be slow and thus may serve as the rate determining step. In general, however, in the presence of the catalyst, the overall rate of the reaction is faster than it would be if the reactants were in the gas or liquid phase., 651780-27-7
An elementary termolecular reaction involves the simultaneous collision of three atoms, molecules, or ions.Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, cas is 651780-27-7,the Benzisoxazole compound. 651780-27-7. Here is a downstream synthesis route of the compound 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., 651780-27-7
Any one of these steps may be slow and thus may serve as the rate determining step. In general, however, in the presence of the catalyst, the overall rate of the reaction is faster than it would be if the reactants were in the gas or liquid phase., 651780-27-7
Reference£º
Patent; MEMORY PHARMACEUTICALS CORPORATION; WO2005/111038; (2005); A2;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics