2-(4-BROMOPHENYL)PROPAN-2-OL

l-(4-Bromophenyl)ethanone (9.25 g, 46.5 mmol) was dissolved in tetrahydrofuran (200 mL). The solution was cooled in a -50 Preparation of Intermediate 2-(4-bromophenyl)propan-2-ol (1AK-1); Dibromobenzene (2g, 8.478mmol) in tetrahydrofuran (25ml_) was cooled to -78°C and n -buthyllithium (2.5 /W in hexane; 3.8ml_, 9.33mmol) was added drop wise and stirred for1 hour. Acetone (591 mg, 10.2mmol) added drop wise and once addition was complete, the reaction was warmed up to 0[0166] To the mixture of 1, 4-dibromobenzene (5.2 g, 22.0mmol) in THF (50 mL) was added dropwise n-BuLi (8.9 mL, 22.0 mmol, 2.5 M) at -60° C. The resulting mixture wasstirred at -60° C. for 1 hr, then a mixture of acetone (3.8 g, 65.5 mmol) in THF (10 mL) was added dropwise at -60° C.After addition, the mixture was allowed to 20° C. slowly.After 1 hr, TLC (PE) showed the starting material was consumedcompletely. The reaction was quenched by sat. NH4Cl(50 mL). The mixture was extracted with EtOAc (50 mL *3).The combined organic layers were dried over Na2S04 andfiltered. After concentration, the residue was purified byMPLC to give the title compound (3.0 g, yield: 63.8percent) as ayellow oil.n-Butyl lithium (2.5 M in hexanes, 6.8 mE, 17.0 mmol) was added dropwise to a stirred and cooled (-78 °C) solution of I , 4-dibromobenzene (4.0 g, 16.9 mmol) in THF (50 mL). Afier addition, stirring at -78 °C was continued for 1 h, and acetone (3, 0 g, 51.7 mmol) was added dropwise. The resulting mixture was warmed to 0 °C and stirred for another 3 h before being quenched by addition of saturated aqueous ammonium chloride (40 mL). The mixture was extracted with 75percent ethyl acetate/petroleum ether (3 x 50 mL). The combined organic extractswere washed with brine (50 mL), dried over sodium sulfate and concentrated under reduced pressure to give title compound (1.8 g, 50percent) as a colorless oil. LCMS MJZ [M-OHj 197.n-Butyl lithium (6.8 n L, 17.0 mmol) was added dropwise to a stirred and cooled (-78 °C) solution of 1 , 4-dibromobenzene (4.0 g, 16.9 mmol) in THF (50 mL). After addition, stirring at 78 °C was continued for 1 h, and acetone (3.0 g, 51.7 mmol) was added dropwise. The resultin mixture was warmed to 0 °C and stirred for another 3 h before being quenched by addition of saturated aqueous ammonium chloride (40 mL). The mixture was extracted with 75percent ethyl acetate/petroleum ether (3 x 50 mL). The combined organic extracts were washed with brine (50 mL), dried over sodium sulfate and concentrated under reduced pressure to give title compound (1.8 g, 50percent yield) as a colorless oil. LCMS M/Z [M-OHTo a solution of methyl 4-bromobenzoate (5 g, 23.25 mmol) in THF (50 mL) at 0°C was added methylmagnesium bromide (23.25 mL, 69.8 mmol) (3M in diethyl ether) dropwise. The resulted mixture was stirred at room temperature for 5 h. Aqueous citricacid (1 M) was added, and the mixture stirred for 1 h, then extracted with ethyl acetate. The organic layer was dried over sodium sulfate, concentrated, and purified by flash column chromatography (80 g silica gel, 20percent-50percent EtOAc/hexanes) to provide the product of Step 1 (4.5 g, 90percent yield) as a colorless oil. LC retention time: 2.63 mm.Preparation 36 2-(4-Bromo-phenvl)-propan-2-ol; A solution of methyl p-bromobenzoate (3g, 13.2 mmol) in tetrahydrofuran (14 mL) cooled to-30°C was treated dropwise with methyl magnesium bromide (1 M in diethyl ether, 105.5 mmol, 105.5 mL). Upon completion of addition, the resulting suspension was allowed to warm to room temperature and was stirred for 5 hours. Saturated aqueous ammonium chloride (100 mL) was added slowly and the mixture was diluted with ethyl acetate (100 mL). The organic and aqueous layers were separated and the aqueous layer was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were dried over magnesium sulfate, were filtered, and the solvent was removed in vacuo. Purification by silica gel chromatography (10: 1 hexanes-ethyl acetate) gave 2.2 g (79percent yield) of 2- (4-bromo-phenyl)-propan-2-ol. 13C NMR (100 MHz, CDCI3) d 148.4, 131. 4, 126.6, 120. 8, 72.5, 31.9 ; MS (AP/CI) 197.1, 199.1 (M+H) +A solution of methyl p-bromobenzoate (3 g, 13.2 mmol) in tetrahydrofuran (14 mL) cooled to -30° C. was treated dropwise with methyl magnesium bromide (1 M in diethyl ether, 105.5 mmol, 105.5 mL). Upon completion of addition, the resulting suspension was allowed to warm to room temperature and was stirred for 5 h. Saturated aqueous ammonium chloride (100 mL) was added slowly and the mixture was diluted with ethyl acetate (100 mL). The organic and aqueous layers were separated and the aqueous layer was extracted with ethyl acetate (3.x.50 mL). The combined organic layers were dried over magnesium sulfate, were filtered, and the solvent was removed in vacuo. Purification by silica gel chromatography (10:1 hexanes-ethyl acetate) gave 2.2 g (79percent yield) of 2-(4-bromo-phenyl)-propan-2-ol. PREPARATION 51; EPO A solution of methyl p-bromobenzoate (3g, 13.2 mmol) in tetrahydrofuran (14 mL) cooled to -30Synthesis of 1-bromo-4-(1-methoxy-1-methyl-ethyl)-benzene:A mixture of 6.87 g of ethyl 4-bromobenzoate (10) was allowed to react with 64 mL(1.4 M in toluene) of methyl magnesium bromide in THF at -4O

Molecular Weight:215.09
XLogP3:2.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:213.99933
Monoisotopic Mass:213.99933
Topological Polar Surface Area:20.2
Heavy Atom Count:11
Complexity:126
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes