methyl 2-(4-chloro-2-fluorophenyl)acetate

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

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

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

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

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

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

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

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

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of palladium acetate (3.3 mg, 0.0146 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (12.0 mg, 0.0293 mmol) and potassium phosphate (62.3 mg, 0.29 mmol) in water (0.050 mL) and toluene (0.200 mL) was stirred for three minutes. A solution of (4-chloro-2-fluoro-phenyl)acetic acid methyl ester (Example 40; 31.8 mg, 0.15 mmol) and (E)-3-ethyl-1-(4-{1-ethyl-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-1-penten-3-ol (Example 39-(5); 50.0 mg, 0.1049 mmol) in toluene (0.250 mL) was added, and the mixture was stirred in a nitrogen atmosphere at 100° C. for 1.5 hours. After filtration through cotton plug, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (17% ethyl acetate/hexane) to give the title compound (40.1 mg, 73%). After filtration through cotton plug the filtrate was concentrated under reduced pressure The residue was purified by silica gel chromatography (17% ethyl acetate/hexane)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (4-Chloro-2-fluoro-phenyl)acetic acid methyl ester (Example 40; 30 mg, 0.149 mmol), palladium acetate (2.2 mg, 0.010 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (8.2 mg, 0.020 mmol), potassium phosphate (63 mg, 0.297 mmol) and water (0.2 mL) were added to a solution of (E)-1-(4-{1-[3,5-dimethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1-ethyl-propyl}-2-methyl-phenyl)-3-ethyl-1-penten-3-ol (Example 38-(6); 50 mg, 0.099 mmol) in toluene (2 mL). After replacement with nitrogen, the mixture was stirred at 100° C. for one hour. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution, followed by extraction with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=4:1) to give the target compound as a colorless oil (32.5 mg, 60%). followed by extraction with dichloromethane The organic layer was dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=4:1)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (4-Chloro-2-fluoro-phenyl)acetic acid methyl ester (Example 40; 30 mg, 0.149 mmol), palladium acetate (2.2 mg, 0.010 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (8.2 mg, 0.020 mmol), potassium phosphate (63 mg, 0.297 mmol) and water (0.2 mL) were added to a solution of (E)-1-(4-{1-[3,5-dimethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1-ethyl-propyl}-2-methyl-phenyl)-3-ethyl-1-penten-3-ol (Example 38-(6); 50 mg, 0.099 mmol) in toluene (2 mL). After replacement with nitrogen, the mixture was stirred at 100° C. for one hour. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution, followed by extraction with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=4:1) to give the target compound as a colorless oil (32.5 mg, 60%). followed by extraction with dichloromethane The organic layer was dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=4:1)