methyl 2-(4-bromophenyl)propanoate

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

Procedure: To a stirred solution of compound 68b (5 g, 0.02 mol) in THF (100 mL) was added a 1 M THF solution of NaHMDS (22.6 mL, 22.6 mmol) at 0° C. under a nitrogen atmosphere. The resulting solution was allowed to warm to room temperature and stirred for 1 h. The reaction mixture was then cooled to 0° C. and iodomethane (3.19 g, 22.5 mmol) was added dropwise. The ice-water bath was removed and stirring was continued for an additional hour at room temperature. The reaction mixture was then treated with water (50 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to afford compound 68c as brown oil. Mass Spectrum (GCMS, ESI pos.): Calcd. for C11H13BrO2: 256.0 (M). found: 256.0. The reaction mixture was then cooled to 0° C. The ice-water bath was removed stirring was continued for an additional hour at room temperature The reaction mixture was then treated with water (50 mL) extracted with EtOAc (3×100 mL) The combined organic layers were dried over anhydrous sodium sulfate filtered the filtrate was concentrated under reduced pressure

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

Procedure: To a stirred solution of compound 68b (5 g, 0.02 mol) in THF (100 mL) was added a 1 M THF solution of NaHMDS (22.6 mL, 22.6 mmol) at 0° C. under a nitrogen atmosphere. The resulting solution was allowed to warm to room temperature and stirred for 1 h. The reaction mixture was then cooled to 0° C. and iodomethane (3.19 g, 22.5 mmol) was added dropwise. The ice-water bath was removed and stirring was continued for an additional hour at room temperature. The reaction mixture was then treated with water (50 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to afford compound 68c as brown oil. Mass Spectrum (GCMS, ESI pos.): Calcd. for C11H13BrO2: 256.0 (M). found: 256.0. The reaction mixture was then cooled to 0° C. The ice-water bath was removed stirring was continued for an additional hour at room temperature The reaction mixture was then treated with water (50 mL) extracted with EtOAc (3×100 mL) The combined organic layers were dried over anhydrous sodium sulfate filtered the filtrate was concentrated under reduced pressure

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

Procedure: To a stirred solution of compound 68a (7.5 g, 0.032 mol) in THF (100 mL), 1 M THF solution of NaHMDS (36 mL, 0.036 mol) was added dropwise at 0 C. The resulting solution was allowed to warm to room temperature and stirred for 1 h before cooling back down to 0° C. The cooled reaction mixture was treated dropwise with iodomethane (5.1 g, 0.035 mol). The ice-water bath was removed and stirring was continued for an additional hour at room temperature. The reaction was then quenched by the addition of water (50 mL). The reaction mixture was extracted with EtOAc (3×100 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to afford compound 68b as a yellow oil. Mass Spectrum (GCMS, ESI pos.): Calcd. for C10H11BrO2: 242.0 (M). found: 242.0. before cooling back down to 0° C The cooled reaction mixture The ice-water bath was removed stirring was continued for an additional hour at room temperature The reaction was then quenched by the addition of water (50 mL) The reaction mixture was extracted with EtOAc (3×100 mL) The combined organic layers were dried over anhydrous sodium sulfate filtered the filtrate was concentrated under reduced pressure

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 2-(4-bromophenyl)propanoate, 7-e, (500 mg, 2.06 mmol), diethylphosphite (994 mg, 7.20 mmol) and triethylamine (681 mg, 6.7 mmol) in toluene (5 mL) was added [1,1′-bis(diphenylphosphino) ferrocene]dicholoropalladium (54 mg). The resulting reaction mixture was heated at 110° C. under nitrogen overnight. The cooled reaction mixture was filtrated (washed with DCM, 3×10 mL), and the filtrate was concentrated to afford the crude product which was purified by column chromatography to give the title compound, 7-f, as yellow brown oil (500 mg, 99%). 1H NMR (300 MHz, CDCl3) δ1.30-1.39 (m, 6H), 1.51 (d, J=7.2 Hz, 3H), 3.67 (s, 3H), 3.77 (q, J=7.2 Hz, 1H), 4.05-4.20 (m, 4H), 7.37-7.41 (m, 2H), 7.72-7.79 (m, 2H). LC-MS (M+H)+ 301. The resulting reaction mixture The cooled reaction mixture was filtrated (washed with DCM, 3×10 mL) the filtrate was concentrated to afford the crude product which was purified by column chromatography