methyl 2-(3-bromo-4-fluorophenyl)acetate

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

Procedure: 3-Bromo-4-fluorophenylacetic acid (2.078 g, 8.92 mmol) and thionyl chloride (1.3 mL, 17.84 mmol) were combined in MeOH (20 mL) and stirred at room temperature for 10 minutes. The mixture was concentrated, and the residue was worked up with CH2Cl2 and 1N aqueous NaOH. The organic layer was dried over MgSO4, filtered, and concentrated to give the title compound. The mixture was concentrated The organic layer was dried over MgSO4 filtered concentrated

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Pd-118 (0.201 g) was dissolved in acetonitrile (20 mL) and stirred for 5 min before addition of potassium carbonate (5.34 g), water (20 mL) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.95 g). The mixture was stirred for a further 5 min then methyl 2-(3-bromo-4-fluorophenyl)acetate [Example 13, Step i)] (3.18 g) in MeCN (2 mL) added and the reaction was heated at the heating block (80° C.) for 25 min. The mixture was cooled and extracted into DCM (100 mL). Organic was separated, dried over magnesium sulfate. Solvents were evaporated to give a brown oil. The crude product was purified by flash silica chromatography, elution gradient 0 to 60% ethyl acetate in isohexane to afford the subtitled compound (3.36 g) as a gum. 1H NMR (300 MHz, CDCl3) δ 7.84 (s, 1H), 7.77 (d, J=2.3 Hz, 1H), 7.44 (dd, J=7.3, 1.5 Hz, 1H), 7.12-7.02 (m, 2H), 3.96 (s, 3H), 3.71 (s, 3H), 3.62 (s, 2H) The mixture was cooled extracted into DCM (100 mL) Organic was separated dried over magnesium sulfate Solvents were evaporated to give a brown oil The crude product was purified by flash silica chromatography, elution gradient 0 to 60% ethyl acetate in isohexane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Pd-118 (0.201 g) was dissolved in acetonitrile (20 mL) and stirred for 5 min before addition of potassium carbonate (5.34 g), water (20 mL) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.95 g). The mixture was stirred for a further 5 min then methyl 2-(3-bromo-4-fluorophenyl)acetate [Example 13, Step i)] (3.18 g) in MeCN (2 mL) added and the reaction was heated at the heating block (80° C.) for 25 min. The mixture was cooled and extracted into DCM (100 mL). Organic was separated, dried over magnesium sulfate. Solvents were evaporated to give a brown oil. The crude product was purified by flash silica chromatography, elution gradient 0 to 60% ethyl acetate in isohexane to afford the subtitled compound (3.36 g) as a gum. 1H NMR (300 MHz, CDCl3) δ 7.84 (s, 1H), 7.77 (d, J=2.3 Hz, 1H), 7.44 (dd, J=7.3, 1.5 Hz, 1H), 7.12-7.02 (m, 2H), 3.96 (s, 3H), 3.71 (s, 3H), 3.62 (s, 2H) The mixture was cooled extracted into DCM (100 mL) Organic was separated dried over magnesium sulfate Solvents were evaporated to give a brown oil The crude product was purified by flash silica chromatography, elution gradient 0 to 60% ethyl acetate in isohexane

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

Procedure: A solution of (diazomethyl)trimethylsilane (12.87 mL) in diethyl ether was added to an ice-batch cooled solution of 2-(3-bromo-4-fluorophenyl)acetic acid (3 g) in dichloromethane (20 mL) and methanol (5 mL). The mixture was stirred for 10 min. and concentrated in vacuo to give methyl 2-(3-bromo-4-fluorophenyl)acetate (3.20 g) that was concentrated in vacuo

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

Procedure: 3-Bromo-4-fluorophenylacetic acid (2.078 g, 8.92 mmol) and thionyl chloride (1.3 mL, 17.84 mmol) were combined in MeOH (20 mL) and stirred at room temperature for 10 minutes. The mixture was concentrated, and the residue was worked up with CH2Cl2 and 1N aqueous NaOH. The organic layer was dried over MgSO4, filtered, and concentrated to give the title compound. The mixture was concentrated The organic layer was dried over MgSO4 filtered concentrated

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

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

Procedure: 3-Bromo-4-fluorophenylacetic acid (2.078 g, 8.92 mmol) and thionyl chloride (1.3 mL, 17.84 mmol) were combined in MeOH (20 mL) and stirred at room temperature for 10 minutes. The mixture was concentrated, and the residue was worked up with CH2Cl2 and 1N aqueous NaOH. The organic layer was dried over MgSO4, filtered, and concentrated to give the title compound. The mixture was concentrated The organic layer was dried over MgSO4 filtered concentrated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Pd-118 (0.201 g) was dissolved in acetonitrile (20 mL) and stirred for 5 min before addition of potassium carbonate (5.34 g), water (20 mL) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.95 g). The mixture was stirred for a further 5 min then methyl 2-(3-bromo-4-fluorophenyl)acetate [Example 13, Step i)] (3.18 g) in MeCN (2 mL) added and the reaction was heated at the heating block (80° C.) for 25 min. The mixture was cooled and extracted into DCM (100 mL). Organic was separated, dried over magnesium sulfate. Solvents were evaporated to give a brown oil. The crude product was purified by flash silica chromatography, elution gradient 0 to 60% ethyl acetate in isohexane to afford the subtitled compound (3.36 g) as a gum. 1H NMR (300 MHz, CDCl3) δ 7.84 (s, 1H), 7.77 (d, J=2.3 Hz, 1H), 7.44 (dd, J=7.3, 1.5 Hz, 1H), 7.12-7.02 (m, 2H), 3.96 (s, 3H), 3.71 (s, 3H), 3.62 (s, 2H) The mixture was cooled extracted into DCM (100 mL) Organic was separated dried over magnesium sulfate Solvents were evaporated to give a brown oil The crude product was purified by flash silica chromatography, elution gradient 0 to 60% ethyl acetate in isohexane

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

Procedure: A solution of (diazomethyl)trimethylsilane (12.87 mL) in diethyl ether was added to an ice-batch cooled solution of 2-(3-bromo-4-fluorophenyl)acetic acid (3 g) in dichloromethane (20 mL) and methanol (5 mL). The mixture was stirred for 10 min. and concentrated in vacuo to give methyl 2-(3-bromo-4-fluorophenyl)acetate (3.20 g) that was concentrated in vacuo