3-Bromo-α-methylbenzeneacetic acid

A solution of LDA in THF/n-heptane/ethylbenzene (1.8M, 23.25 mL, 41.85 mmol) is cooled down to -78°C and added a solution of 3-bromophenylacetic acid [3 g, 13.95 mmol, Intermediate (68)] in THF (7 mL) dropwise over 15 minutes. The mixture is stirred for 1 h at -78°C and treated dropwise with methyl iodide (6.34 g, 44.64 mmol) over 15 minutes. The reaction mixture is warmed up to room temperature and after stirring overnight, the mixture is quenched with 2N hydrochloric acid and concentrated to remove THF. The residue is diluted with ether, washed twice with 2 N hydrochloric acid (20 mL) and extracted twice with 10percent sodium hydroxide (20 mL). The combined sodium hydroxide extracts are acidified with 6 N hydrochloric acid to pH=l and extracted three times with ether (50 mL). Combined organic extracts are washed with brine, dried over sodium sulfate and concentrated to obtain 2-f3-bromo-phenyl)-propionic acid [3 g, 100percent, Intermediate (69)] as a solid, which is used without further purification. LC/MS: 229 (M+H).A solution of LDA in THF/n-heptane/ethylbenzene (1.8M, 23.25 mL, 41.85 mmol) is cooled down to -78°C and added a solution of 3-bromophenylacetic acid [3 g, 13.95 mmol, Intermediate (68)] in THF (7 mL) dropwise over 15 minutes. The mixture is stirred for 1 h at -78°C and treated dropwise with methyl iodide (6.34 g, 44.64 mmol) over 15 minutes. The reaction mixture is warmed up to room temperature and after stirring overnight, the mixture is quenched with 2N hydrochloric acid and concentrated to remove THF. The residue is diluted with ether, washed twice with 2 N hydrochloric acid (20 mL) and extracted twice with 10percent sodium hydroxide (20 mL). The combined sodium hydroxide extracts are acidified with 6 N hydrochloric acid to pH=l and extracted three times with ether (50 mL). Combined organic extracts are washed with brine, dried over sodium sulfate and concentrated to obtain 2-f3-bromo-phenyl)-propionic acid [3 g, 100percent, Intermediate (69)] as a solid, which is used without further purification. LC/MS: 229 (M+H).To a solution of diisopropylamine (0.97 g, 9.6 mmol) in THF (20 mL) at room temperature was added n-butyl lithium (2.5 N in hexane, 4 mL, 10 mmol) and the resulting solution was stirred at room temperature for 15 minutes. To above solution was added a solution of 3-bromophenylacetic acid (1.0 g, 4.6 mmol) in THF (10 mL) dropwise at room temperature and the stirring was continued for another 15 minutes. Methyl iodide (1.49 g, 10.5 mmol) was added and the resulting mixture was stirred at room temperature for 15 minutes. Satuated sodium chloride (30 mL) was added and the aqueous phase was adjusted to pH 5 by addition of hydrochloric acid (1 N). The resulting mixture was extracted with ethyl acetate (20 mL.x.3) and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel using a gradient of formic acid and methanol in dichloromethane to afford 2-(3-bromo-phenyl)-propionic acid (890 mg, 84percent) as a white solid. MS: m/z 229 (M+HGeneral procedure: Step 1. To a solution of 3-bromophenylacetic acid (1.30 g, 6 mmol) (azeotroped with toluene) in 2 mL of dry toluene was added sodium bis(trimethylsilyl)amide (14 mL of 1N solution in THF, 14 mmol). After stirring at room temperature for 20 min, methyl iodide (0.9 g, 7 mmol) was added dropwise. After 10 min, the reaction was quenched with 2 N HCl to pH = 2, extracted with EtOAc, dried over Na49(a)Step 1. A solution of LDA in THF/n-heptane/ethylbenzene (1.8M, 23.25 mL, 41.85 ramol) is cooled down to -78°C and added a solution of 3-bromophenylacetic acid [3 g, 13.95 mmol, Intermediate (68)] in THF (7 mL) dropwise over 15 minutes. The mixture is stirred for 1 h at -780C and treated dropwise with methyl iodide (6.34 g, 44.64 mmol) over 15 minutes. The reaction mixture is warmed up to room temperature and after stirring overnight, the mixture is quenched with 2N hydrochloric acid and concentrated to remove THF. The residue is diluted with ether, washed twice with 2 N hydrochloric acid (20 mL) and extracted twice with 10percent sodium hydroxide (20 mL). The combined sodium hydroxide extracts are acidified with 6 N hydrochloric acid to pH=l and extracted three times with ether (50 mL). Combined organic extracts are washed with brine, dried over sodium sulfate and concentrated to obtain 2-(3-bromo-phenyl)-propionic acid [3 g, 100percent, Intermediate (69)] as a solid, which is used without further purification. LC/MS: 229 (M+H).

Molecular Weight:229.07
XLogP3:2.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:227.97859
Monoisotopic Mass:227.97859
Topological Polar Surface Area:37.3
Heavy Atom Count:12
Complexity:170
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes