(2,5-dichlorophenyl)boronic acid

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:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from a Suzuki coupling of 4-Methyl-2-(5-trifluoromethanesulfonyloxy-4′-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester (intermediate Example 1g) with 2,5-dichloro-phenylboronic acid under the conditions described in Example 1; 1H NMR (400 MHz, MeOD) δ ppm 0.97-1.08 (m, 6H), 1.59 (dd, J=13.33, 6.72 Hz, 1H), 1.78 (dt, J=13.76, 6.94 Hz, 1H), 2.04 (dd, J=13.45, 7.34 Hz, 1H), 3.85 (t, J=7.70 Hz, 1H), 7.39-7.87 (m, 10H); Calcd for C25H21Cl2F302 (M+Na) 503.09, Found 503.

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: Following the general Suzuki coupling procedure, reaction of bromide 5A (75 mg, 0.25 mmol), 2,5-dichlorophenylboronic acid (58 mg, 0.30 mmol), K2CO3 (105 mg, 0.75 mmol) and Pd(PPh3)4 (5.8 mg, 0.005 mmol) provided the coupling product as a white powder (23 mg, 25% yield). EIMS 360.0 [M+H]+.

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

Procedure: Following the general Suzuki coupling procedure, reaction of bromide 5A (75 mg, 0.25 mmol), 2,5-dichlorophenylboronic acid (58 mg, 0.30 mmol), K2CO3 (105 mg, 0.75 mmol) and Pd(PPh3)4 (5.8 mg, 0.005 mmol) provided the coupling product as a white powder (23 mg, 25% yield). EIMS 360.0 [M+H]+.

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

Procedure: To a solution of [(R)-8-bromo-6-fluoro-3,4-dihydro-2H-chromen-2-yl)methyl 4-methylbenzenesulfonate, prepared in Example 38, step 2 (0.40 g, 0.97 mmol) and 2,5-dichlorophenylboronic acid (0.56 g, 2.9 mmol) in dioxane (10 ml) was added a solution of potassium carbonate (0.34 g, 2.4 mmol) in water (2 mL) and the mixture purged with nitrogen for 20 minutes. Dichlorobis(tri-o-tolylphosphine)palladium (II) (20 mg, 0.029 mmol) was added and the reaction mixture heated to reflux for 1 hour. The cooled reaction mixture was then partitioned between ethyl acetate (100 mL) and 2.0 M aqueous sodium hydroxide (100 mL). The organic layer was separated, washed with water (100 mL) and saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford a yellow syrup. Purification by flash chromatography using a solvent gradient of 5 to 20% ethyl acetate in hexane gave 0.41 g (88%) of ((R)-8-(2,5-dichlorophenyl)-6-fluoro-2H-chromen-2-yl)methyl 4-methylbenzenesulfonate as a colorless oil. MS (ES) m/z 496.0 ([M+NH4]+). the mixture purged with nitrogen for 20 minutes the reaction mixture heated to reflux for 1 hour The cooled reaction mixture was then partitioned between ethyl acetate (100 mL) and 2.0 M aqueous sodium hydroxide (100 mL) The organic layer was separated washed with water (100 mL) and saturated brine (100 mL) dried over anhydrous sodium sulfate filtered concentrated under reduced pressure to afford a yellow syrup Purification by flash chromatography

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

Procedure: A mixture of ((2R)-8-{[(trifluoromethyl)sulfonyl]oxy}-3,4-dihydro-2H-chromen-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.1 mmol), 2,5-dichlorophenylboronic acid (0.42 g, 2.2 mmol), potassium carbonate (0.46 g, 3.3 mmol) and lithium chloride (0.14 g, 3.3 mmol) in dioxane (3.75 ml) and water (1.25 mL) was purged with nitrogen for 30 minutes. Tetrakis(triphenylphosphine)palladium (0) (60 mg, 0.052 mmol) was added and the reaction mixture heated at 100° C. for 4 hours. The cooled reaction mixture was then partitioned between ethyl acetate (15 mL) and 1 M aqueous sodium hydroxide (15 mL). The organic layer was separated, washed with saturated brine (15 mL) dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford an orange oil. Purification by flash chromatography using a solvent gradient of 5 to 20% ethyl acetate in hexane gave 0.46 g (90%) of [(2R)-8-(2,5-dichlorophenyl)-3,4-dihydro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate as an off-white solid. HRMS: calcd for C23H20Cl2O4S+H+, 463.05321. found (ESI, [M+H]+), 463.0553. was purged with nitrogen for 30 minutes The cooled reaction mixture was then partitioned between ethyl acetate (15 mL) and 1 M aqueous sodium hydroxide (15 mL) The organic layer was separated washed with saturated brine (15 mL) dried over magnesium sulfate filtered concentrated under reduced pressure to afford an orange oil Purification by flash chromatography

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

Procedure: A mixture of ((2R)-8-{[(trifluoromethyl)sulfonyl]oxy}-3,4-dihydro-2H-chromen-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.1 mmol), 2,5-dichlorophenylboronic acid (0.42 g, 2.2 mmol), potassium carbonate (0.46 g, 3.3 mmol) and lithium chloride (0.14 g, 3.3 mmol) in dioxane (3.75 ml) and water (1.25 mL) was purged with nitrogen for 30 minutes. Tetrakis(triphenylphosphine)palladium (0) (60 mg, 0.052 mmol) was added and the reaction mixture heated at 100° C. for 4 hours. The cooled reaction mixture was then partitioned between ethyl acetate (15 mL) and 1 M aqueous sodium hydroxide (15 mL). The organic layer was separated, washed with saturated brine (15 mL) dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford an orange oil. Purification by flash chromatography using a solvent gradient of 5 to 20% ethyl acetate in hexane gave 0.46 g (90%) of [(2R)-8-(2,5-dichlorophenyl)-3,4-dihydro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate as an off-white solid. HRMS: calcd for C23H20Cl2O4S+H+, 463.05321. found (ESI, [M+H]+), 463.0553. was purged with nitrogen for 30 minutes The cooled reaction mixture was then partitioned between ethyl acetate (15 mL) and 1 M aqueous sodium hydroxide (15 mL) The organic layer was separated washed with saturated brine (15 mL) dried over magnesium sulfate filtered concentrated under reduced pressure to afford an orange oil Purification by flash chromatography