2-bromo-1,3-dichlorobenzene

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:; See reaction.notes.procedure_details.

Procedure: 1-Bromo-2,6-dichlorobenzene (90 mg,-0.40 mmol) reacted with 2-methylphenylboronic acid (82 mg, 0.60 mmol) using 2/4 mol % of Pd(dba)2/Ph5FcP(t-Bu)2 and K3PO4 (254 mg, 1.20 mmol) in toluene at 100° C. to give the title compound (88 mg, 76%): 1H-NMR (400 MHz, CDCl3): δ 8.07 (d, 2H, J=8.07 Hz), 7.28-7.18 (m, 3H), 7.15 (t, 1H, J=8.13 Hz), 7.00 (d, 1H, J=7.25 Hz), 1.99 (s, 3H). 13C{1H}-NMR (125 MHz, CDCl3): δ 139.23, 136.91, 136.16, 135.09, 129.90, 129.04, 129.01, 128.39, 127.88, 125.81, 19.30. GC/MS(EI): (M+). at 100° C.

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Bromo-2,6-dichlorobenzene (2.00 g) was dissolved in freshly distilled THF (7 mL). This solution was cooled to −78° C. and n-BuLi (8.3 mL of a 1.6M solution in hexane) was added dropwise to the cold solution under N2. The mixture was stirred for 5 min at −78° C. and (MeO)3B (2.2 mL) was added. The resulting mixture was allowed to warm to room temperature and stirred overnight. Water was added and the resulting mixture was stirred for 0.5 h, then acidified with HOAc and extracted with EtOAc. The organic layer was further washed with water and brine, dried (MgSO4) filtered and evaporated to yield 2,6-dichlorobenzeneboronic acid (1.6 g) to warm to room temperature stirred overnight the resulting mixture was stirred for 0.5 h extracted with EtOAc The organic layer was further washed with water and brine dried (MgSO4) filtered evaporated

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,6-dichlorobromobenzene (3.5 g, 15.7 mmol) and sodium hydroxide (3.14 g, 78.5 mmol) in DME-water (2:1) was added 5-fluoro-2-methoxybenzene boronic acid (4.0 g, 23.5 mmol) at 90° C., followed by tetrakis(triphenylphosphine)palladium (0) (0.9 g, 0.78 mmol). The reaction mixture was heated at 90° C. overnight and cooled to room temperature. The mixture was extracted with methylene chloride and washed with water. The organic solvent was removed under vacuum. Chromatography with 5% ethyl acetate in hexanes afforded 2.62 g (87%) of 2′,6′-dichloro-5-fluoro-2-methoxybiphenyl as a colorless oil. MS (EI) m/z 270 (M+). cooled to room temperature The mixture was extracted with methylene chloride washed with water The organic solvent was removed under vacuum

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,6-dichlorobromobenzene (3.5 g, 15.7 mmol) and sodium hydroxide (3.14 g, 78.5 mmol) in DME-water (2:1) was added 5-fluoro-2-methoxybenzene boronic acid (4.0 g, 23.5 mmol) at 90° C., followed by tetrakis(triphenylphosphine)palladium (0) (0.9 g, 0.78 mmol). The reaction mixture was heated at 90° C. overnight and cooled to room temperature. The mixture was extracted with methylene chloride and washed with water. The organic solvent was removed under vacuum. Chromatography with 5% ethyl acetate in hexanes afforded 2.62 g (87%) of 2′,6′-dichloro-5-fluoro-2-methoxybiphenyl as a colorless oil. MS (EI) m/z 270 (M+). cooled to room temperature The mixture was extracted with methylene chloride washed with water The organic solvent was removed under vacuum

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

Procedure: A mixture of 1-bromo-2,6-dichlorobenzene (5.0 g, 0.022 mol), 2-methoxyphenylboronic acid (5.045 g, 0.033 mol) and potassium carbonate (7.65 g, 0.055 mol) in dioxane (130 mL) and water (13 mL) was purged with nitrogen for 20 minutes. Trans-dichlorobis(tri-o-tolylphosphine)palladium (II) (0.87 g, 0.0011 mol) was added and the reaction mixture heated to 100° C. for 36 hours. The cooled reaction mixture was then filtered through celite washing the filter cake with ethyl acetate. The combined organic filtrates were diluted to 500 mL by the addition of ethyl acetate, then washed with 2.0 M aqueous sodium hydroxide (2×350 mL), water (350 mL) and saturated brine (350 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford a yellow oil. Purification by flash chromatography using a solvent gradient of 0.5 to 2% ethyl acetate in hexane gave 2.74 g (49%) of 2′,6′-dichloro-1,1′-biphenyl-2-yl methyl ether as a white solid. MS (EI) m/z 252 (M+). was purged with nitrogen for 20 minutes The cooled reaction mixture was then filtered through celite washing the filter cake with ethyl acetate The combined organic filtrates were diluted to 500 mL by the addition of ethyl acetate washed with 2.0 M aqueous sodium hydroxide (2×350 mL), water (350 mL) and saturated brine (350 mL) dried over magnesium sulfate filtered concentrated under reduced pressure to afford a yellow oil Purification by flash chromatography

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

Procedure: A mixture of 1-bromo-2,6-dichlorobenzene (5.0 g, 0.022 mol), 2-methoxyphenylboronic acid (5.045 g, 0.033 mol) and potassium carbonate (7.65 g, 0.055 mol) in dioxane (130 mL) and water (13 mL) was purged with nitrogen for 20 minutes. Trans-dichlorobis(tri-o-tolylphosphine)palladium (II) (0.87 g, 0.0011 mol) was added and the reaction mixture heated to 100° C. for 36 hours. The cooled reaction mixture was then filtered through celite washing the filter cake with ethyl acetate. The combined organic filtrates were diluted to 500 mL by the addition of ethyl acetate, then washed with 2.0 M aqueous sodium hydroxide (2×350 mL), water (350 mL) and saturated brine (350 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford a yellow oil. Purification by flash chromatography using a solvent gradient of 0.5 to 2% ethyl acetate in hexane gave 2.74 g (49%) of 2′,6′-dichloro-1,1′-biphenyl-2-yl methyl ether as a white solid. MS (EI) m/z 252 (M+). was purged with nitrogen for 20 minutes The cooled reaction mixture was then filtered through celite washing the filter cake with ethyl acetate The combined organic filtrates were diluted to 500 mL by the addition of ethyl acetate washed with 2.0 M aqueous sodium hydroxide (2×350 mL), water (350 mL) and saturated brine (350 mL) dried over magnesium sulfate filtered concentrated under reduced pressure to afford a yellow oil Purification by flash chromatography

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

Procedure: 1-Bromo-2,6-dichlorobenzene (90 mg,-0.40 mmol) reacted with 2-methylphenylboronic acid (82 mg, 0.60 mmol) using 2/4 mol % of Pd(dba)2/Ph5FcP(t-Bu)2 and K3PO4 (254 mg, 1.20 mmol) in toluene at 100° C. to give the title compound (88 mg, 76%): 1H-NMR (400 MHz, CDCl3): δ 8.07 (d, 2H, J=8.07 Hz), 7.28-7.18 (m, 3H), 7.15 (t, 1H, J=8.13 Hz), 7.00 (d, 1H, J=7.25 Hz), 1.99 (s, 3H). 13C{1H}-NMR (125 MHz, CDCl3): δ 139.23, 136.91, 136.16, 135.09, 129.90, 129.04, 129.01, 128.39, 127.88, 125.81, 19.30. GC/MS(EI): (M+). at 100° C.

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

Procedure: 1-Bromo-2,6-dichlorobenzene (90 mg,-0.40 mmol) reacted with 2-methylphenylboronic acid (82 mg, 0.60 mmol) using 2/4 mol % of Pd(dba)2/Ph5FcP(t-Bu)2 and K3PO4 (254 mg, 1.20 mmol) in toluene at 100° C. to give the title compound (88 mg, 76%): 1H-NMR (400 MHz, CDCl3): δ 8.07 (d, 2H, J=8.07 Hz), 7.28-7.18 (m, 3H), 7.15 (t, 1H, J=8.13 Hz), 7.00 (d, 1H, J=7.25 Hz), 1.99 (s, 3H). 13C{1H}-NMR (125 MHz, CDCl3): δ 139.23, 136.91, 136.16, 135.09, 129.90, 129.04, 129.01, 128.39, 127.88, 125.81, 19.30. GC/MS(EI): (M+). at 100° C.