ethyl 2-(4-bromophenyl)-2-oxoacetate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add LHMDS in THF (451 mL, 1.0 M, 451 mmol) to a slurry of cyclohexylmethyl-triphenyl-phosphonium bromide (207.5 g, 472 mmol) in THF (500 mL) maintained at 0 ° C. and stir the mixture for 1 h. Dissolve (4-bromo-phenyl)-oxo-acetic acid ethyl ester (prepared as described by Hu, Shengkui; Neckers, Douglas C. J. Org. Chem. 1996, 61, 6407-6415.) in THF (40 mL) and add the resulting solution to the reaction mixture. Stir the reaction mixture for 60 h at room temperature. Dilute the mixture with water and neutralize with 1 N HCl. Evaporate the THF and add ether (700 mL). Stir at room temperature for 30 minutes and filter through celite®. Separate the layers and extract the aqueous layers with ether. Dry the combined organic layers over magnesium sulfate, filter, and concentrate. If large amounts of triphenylphosphine oxide are present, add ether (1 L), filter through celite® and concentrate the filtrate. Dissolve the brown oil in CH2Cl2 (50 mL) and filter through a pad of silica gel, eluting with a gradient of 0-5% EtOAc in hexanes to obtain the title compound (109.7 g) as an E/Z mixture (E/Z ratio: 2/1). MS (m/e): 337 (+H). Stir the reaction mixture for 60 h at room temperature Evaporate the THF add ether (700 mL) Stir at room temperature for 30 minutes filter through celite® Separate the layers extract the aqueous layers with ether Dry the combined organic layers over magnesium sulfate filter concentrate add ether (1 L) filter through celite® concentrate the filtrate Dissolve the brown oil in CH2Cl2 (50 mL) filter through a pad of silica gel eluting with a gradient of 0-5% EtOAc in hexanes

Conditions: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl-4-bromobenzoylformate (940 mg) and 2-chloroethanol (0.360 mL) in a 2:1 mixture of dimethylformamide:tetrahydrofuran (2.1 mL) was added dropwise at −60° C. a solution of potassium tert-butanol (0.597 mg) in dimethylformamide (2 mL). The reaction mixture was stirred at −60° C. for 4 h then allowed to warm up to room temperature and stirred at room temperature overnight. The reaction mixture was partitioned between an aqueous solution of ammonium chloride and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic layer were washed with brine. The crude mixture was concentrated to dryness and purified by chromatography on silica gel to yield the title compound as a colorless liquid (616 mg; 58%). MS (ESI): m/z=300.8 [M+H]+. to warm up to room temperature stirred at room temperature overnight The reaction mixture was partitioned between an aqueous solution of ammonium chloride and ethyl acetate The aqueous layer was extracted with ethyl acetate the combined organic layer were washed with brine The crude mixture was concentrated to dryness purified by chromatography on silica gel