4'-Bromo-3'-methylacetophenone

l-(4-bromo-3-methylphenyl)ethanone. l-(4-bromo-3-methylphenyl)ethanol (2.14 g, 9.9 mmol) and pyridinium chlorochromate (2.62 g, 12 mmol) were added to a solution of dichloromethane (30 mL) under nitrogen atmosphere. And the reaction was stirred at room temperature for 12 hours. The mixture was partitioned between dichloromethane (3 * 20 mL) and brine (20 mL). The organic layer was concentrated to dryness and the residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate = 30: 1) to give l-(4-bromo- 3-methylphenyl) ethanone (2.08 g, 99percent) as a colorless oil. LRMS (M + H+) mlz: calcd 211.98; found 211. 1H NMR (300 MHz, CDC13): ^ 7.81 (s, 1H), 7.62-7.61 (m, 2H), 2.58 (s, 3H), 2.46 (s, 3H).1-(4-bromo-3-methylphenyl)ethanol (2.14 g, 9.9 mmol) and pyridinium chlorochromate (2.62 g, 12 mmol) were added to a solution of dichloromethane (30 mL) under nitrogen atmosphere. And the reaction was stirred at room temperature for 12 hours. The mixture was partitioned between dichloromethane (3*20 mL) and brine (20 mL). The organic layer was concentrated to dryness and the residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=30:1) to give 1-(4-bromo-3-methylphenyl)ethanone (2.08 g, 99percent) as a colorless oil. LRMS (M+HStep 2: Synthesis of 4'-bromo-3'-methylacetophenone 27.0 g of acetonitrile was added to a sulfuric acid solution of 27.0 g (181 mmol) of 4-acetyl-2-methylaniline, and the mixture was cooled to 0°C. An aqueous solution in which 13.1 g (190 mmol) of sodium nitrite was dissolved into 26.2 g of water was added in dropwise to the mixture. After reacting the resultant mixture for 1 hour at 0°C, an aqueous solution in which 1.1 g (18 mmol) of urea was dissolved into 2.2 g of water was added in dropwise, and the mixture was further stirred for 30 minutes to obtain an aqueous solution of 4-acetyl-2-methylbenzenediazonium sulfate. 5.18 g (36 mmol) of copper bromide, 62.2 g (362 mmol) of 47percent hydrobromic acid and 81.0 g of acetonitrile were fed into another reactor. The aqueous solution of 4-acetyl-2-methylbenzenediazonium sulfate was added to this mixture in dropwise over 1 hour with stirring at 50°C. After adding in dropwise, the mixture was reacted for 1 hour at 50°C. Then, 81 g of toluene was added and the mixture was stirred for 30 minutes, and the water phase was separated. 54 g of toluene was added to the water phase and extracted again. The combined toluene solution was washed twice with 54 g of 14percent aqueous ammonia and once with 54 g of water to obtain a toluene solution of 4'-bromo-3'-methylacetophenone. After removing the solvent by distilling under reduced pressure, the residue was distilled under reduced pressure of 1.5 kPa. 32.8 g of the obtained fraction which was collected in the range of outflow gas temperature from 130°C to 137°C was analyzed by HPLC. A percentage of relative area of 4'-bromo-3'-methylacetophenone was 99.1 percent (yield 84percent).Take 3-methyl-4-aminoacetophenone 149g, Add 500g concentrated hydrochloric acid, -10 ° ~ -5 °, An aqueous solution of sodium nitrite 140g (70g of sodium nitrite + 70g of water) was added dropwise during the addition.The temperature must not exceed -5° after the additionContinue to react for 30min. After the reaction is over, The reaction solution was slowly added dropwise to the aqueous solution of cuprous bromide (150 g copper bromide + 200 g water).The reaction system slowly warms up to 70 degrees for 2 hours. After the reaction is completed, it is filtered and the cake is washed to neutrality.The pale yellow solid was 171 g in a yield of 81percent.4-bromo-3-methylacetophenonone 4-bromo-3-methylbenzonitrile (lg, 5.1 mmol) was dissolved in toluene (4 mL) under argon atmosphere. Methyl magnesium bromide (1.3 mL, 1 1.22 mmol) was added to the solution. The mixture was heated at 60-65 °C overnight. The reaction mixture was hydrolyzed with a 5M HPREPARATION At ambient temperature, methylmagnesium iodide (3 M in diethyl ether) (17 mL, 51 mmoles) is added dropwise to a solution of commercial 4-bromo-3-methylbenzonitrile (10 g, 51 mmoles) in diethyl ether (100 mL). The reaction mixture is heated at reflux for 16 hours. After return to ambient temperature, 60 mL of 6N hydrochloric acid are added, and the mixture is then heated at reflux for 6 hours. After cooling, the aqueous and organic phases are separated, and the aqueous phase is extracted with 40 mL of ethyl acetate. The organic phases are combined, washed with a saturated aqueous NaCl solution (2×40 mL), dried over MgSOAt ambient temperature, methylmagnesium iodide (3 M in diethyl ether) (17 mL, 51 mmoles) is added dropwise to a solution of commercial 4-bromo-3-methylbenzonitrile (10 g, 51 mmoles) in diethyl ether (100 mL). The reaction mixture is heated at reflux for 16 hours. After return to ambient temperature, 60 mL of 6N hydrochloric acid are added, and the mixture is then heated at reflux for 6 hours. After cooling, the aqueous and organic phases are separated, and the aqueous phase is extracted with 40 mL of ethyl acetate. The organic phases are combined, washed with a saturated aqueous NaCl solution (2×40 mL), dried over MgSO4 and then concentrated under reduced pressure. 4.5 g of intermediate 9 are obtained in the form of a brown oil. 1H NMR (300 MHz, CDCl3): delta 7.80 (s, 1H), 7.62 (s, 2H), 2.60 (s, 3H), 2.45 (s, 3H) IR (cm-1): 1681Aluminum chloride (9.5 g) was added in portion wise at 0 C to a stirred solution of 2-bromotoluene (formula 3a, 10 g) in dichloromethane and stirred for 10 minutes. Then, acetyl chloride (5.5 g) was added drop wise at the same temperature. The resulting mixture was stirred for 2 hours while cooling with ice. Then the reaction mixture was added to 100 mL of 10 % aq. hydrochloric acid solution, which was then allowed to separate into aqueous and organic layers. The organic layer thus obtained was washed with a 5 % aqueous solution of sodium carbonate and dried over anhydrous sodium sulfate. The organic layer was concentrated and the obtained crude material was purified by fractional distillation to afford (1g)Soluble in 20mL ethylene glycol dimethyl ether, Cool to -10 C and add 1-(isocyanatosulfonyl)-4-methylbenzene (1.37 g).Stirring was continued for 10 minutes at -10 C.Then a solution of potassium tert-butoxide (1 g) in tert-butanol (100 mL) was added.After stirring for 10 minutes, it was stirred at room temperature overnight.After the reaction was completed, 100 mL of ethyl acetate was added, and the mixture was washed with brine.After drying, concentrate under reduced pressure.The residue was separated by silica gel column chromatography (EtOAc:EtOAc:EtOAc2-(4-Bromo-3-methylphenyl)propanenitrile (604 mg) was obtained.

Molecular Weight:213.07
XLogP3:3.3
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:211.98368
Monoisotopic Mass:211.98368
Topological Polar Surface Area:17.1
Heavy Atom Count:11
Complexity:156
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes