27387-23-1, name is 2-(2-Bromo-5-methoxyphenyl)acetonitrile, belongs to nitriles-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. 27387-23-1
D. N, N-DIMETHYL-5-METHOXY-2-BROMOPHENYLACETAMIDE 5-Methoxy-2-bromobenzoic acid (85 g, 0.37 mol) is dissolved in anhydrous THF (100 mL) and cooled in an ice-salt bath until the temperature REACHES-5 C. Borane-THF complex is added dropwise as a 1.0 M solution in THF (736 mL, 0.74 mol) AT-5C. After addition is complete, the reaction mixture is slowly warmed to room temperature and stirred for 12 hours. Water (40 mL) is slowly added dropwise and the reaction mixture stirred for 30 minutes. Additional water (350 mL) is added and the mixture is concentrated by rotary evaporator to remove most of the THF. The remaining material is extracted with EtOAc (800 mL). The organic layer is washed with saturated NAHCO3 (500 mL), brine (250 mL) and then dried (NA2SO4). UPON REMOVAL of the solvent by rotary evaporator, 5-methoxy-2- bromobenzyl alcohol is obtained as a white solid. 5-Methoxy-2-bromobenzyl alcohol (79.5 g, 0.37 mol) is dissolved in 48% HBr (400 mL) and heated to reflux temperature for 4 hours. The reaction mixture is cooled to room temperature and poured into water (1500 mL). The solution is extracted with EtOAc (2 x 500 mL). The combined organic layers are dried (MGS04) and concentrated by rotary evaporator. The crude material is then purified using flash chromatography (CH2CI2/hexanes, from 1: 1 to 4: 1) to give 5-methoxy-2-bromobenzyl bromide. 5-METHOXY-2-BROMOBENZYL bromide (72.8 g, 0.26 mol) is dissolved in EtOH (280 mL) and stirred at room temperature. Sodium cyanide (38.2 g, 0.78 mol) is dissolved in water and added to the solution of the bromide. The reaction mixture is heated to reflux temperature for 3 hours and then cooled to room temperature. Most of the ethanol is removed by rotary evaporator. A solid forms which is isolated by filtration and washed with water (500 mL). The crude material is purified using flash chromatography (CH2CI2/HEXANES, 1: 1) to give 5-methoxy-2-bromophenylacetonitrile (53 g). 5-Methoxy-2-bromophenylacetonitrile (52.8 g, 0.23 mol) is dissolved in ethanol (250 mL) and stirred at room temperature. Sodium hydroxide (9.3 g, 0.47 mol) is dissolved in water (150 mL) and added to the solution of the nitrile. The mixture is heated to reflux temperature for 12 hours and then cooled to room temperature. Most of the ethanol is removed using a rotary evaporator and the residual aqueous solution adjusted to pH 4 with 3 N HCI. The solid which forms is isolated by filtration and washed with water. Air drying gives 5-methoxy-2-bromophenylacetic acid. 5-Methoxy-2-bromophenylacetic acid (56 g, 0.23 mol) is dissolved in CH2CI2 (350 mL) and a catalytic amount of DMF is added and the solution stirred and cooled to 0C. Thionyl chloride (41 mL, 0.34 mol) is added dropwise. The reaction mixture is heated at reflux temperature overnight and then cooled to room temperature. Solvents are removed by rotary evaporator. Twice benzene (500 mL) is added to the residual oil and the benzene solution is evaporated by rotary evaporator to remove any additional volatile components. The residual oil is crystallized from hexanes to give 5-methoxy-2-bromophenylacetyl chloride. 5-Methoxy-2-bromophenylacetyl chloride (60 g, 0.23 mol) is dissolved in anhydrous ET20 (400 mL), stirred and cooled in an ice bath. A 2 M solution of DIMETHYLAMINE (228 mL, 0.46 mol) is added dropwise and the mixture allowed to warm to room temperature and stirred for 2 hours. Additional ET20 (500 mL) is added. The organic solution is washed with 1 N HCI (2 x 500 mL), saturated NAHCO3 (500 mL) and brine (500 mL). The organic layer is dried (NA2SO4) and concentrated by rotary evaporator. The residue is purified using flash chromatography (hexanes/EtOAc, from 7: 3 to 1: 9). Trituration of the crude product with ET20/HEXANES gives N, N-DIMETHYL-5-METHOXY-2-BROMOPHENYLACETAMIDE AS a white crystalline solid (m. p. 88-90C).
Statistics shows that 27387-23-1 is playing an increasingly important role. we look forward to future research findings about 2-(2-Bromo-5-methoxyphenyl)acetonitrile.
Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2004/48314; (2004); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts