4-bromo-1-fluoro-2-phenylmethoxybenzene

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

Procedure: To a solution of 1-methyl-1H-pyrazole-5-boronic acid pinacol ester (1058.42 mg, 5.09 mmol) in MeCN (40 mL) and water (10 mL) was added 2-benzyloxy-4-bromo-1-fluoro-benzene [CAS: 1036724-54-5](1300 mg, 4.62 mmol), sodium carbonate (1470.8 mg, 13.88 mmol) and bis(triphenylphosphine)palladium (II) dichloride (164.24 mg, 0.2300 mmol). The reaction was then heated at 100° C. for 4 hours. The cooled reaction mixture was poured into EtOAc (70 mL) and water (100 mL). The organics were separated, and washed with brine (75 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was then purified over silica (25 g, SNAP cartridge), eluting with EtOAc in isohexane from 0% to 40%. Fractions containing desired product were combined and concentrated in vacuo to give 5-(3-benzyloxy-4-fluoro-phenyl)-1-methyl-pyrazole (D82) (1026.5 mg, 3.4543 mmol, 74.7% yield) as a colourless oil; The cooled reaction mixture The organics were separated washed with brine (75 mL) dried over MgSO4 filtered concentrated in vacuo The residue was then purified over silica (25 g, SNAP cartridge) eluting with EtOAc in isohexane from 0% to 40% Fractions containing desired product concentrated in vacuo

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

Procedure: To a solution of 2-benzyloxy-4-bromo-1-fluoro-benzene [CAS: 1036724-54-5](1250 mg, 4.45 mmol) in MeCN (40 mL) and water (10 mL) was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 h-pyrazole (925.18 mg, 4.45 mmol), sodium carbonate (1414.18 mg, 13.34 mmol) and bis(triphenylphosphine)palladium (II) dichloride (157.92 mg, 0.2200 mmol). The reaction was then heated at 100° C. for 4 hours. The reaction mixture was poured into EtOAc (100 mL) and aq NaOH (0.5M, 200 mL). The organics were separated, and washed with brine (75 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was then purified over silica (25 g, SNAP cartridge), eluting with between 0% and 40% EtOAc in isohexane. Fractions containing the desired product were combined and concentrated in vacuo to give 4-(3-benzyloxy-4-fluoro-phenyl)-1-methyl-pyrazole (D78) (760 mg, 2.5575 mmol, 57.6% yield) as a colourless oil; The organics were separated washed with brine (75 mL) dried over MgSO4 filtered concentrated in vacuo The residue was then purified over silica (25 g, SNAP cartridge) eluting with between 0% and 40% EtOAc in isohexane Fractions containing the desired product concentrated in vacuo

Conditions: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a microwave vial containing 2-benzyloxy-4-bromo-1-fluoro-benzene [CAS: 1036724-54-5] (1500 mg, 5.34 mmol) and (1S,2S)-(+)-1,2-diaminocyclohexane (121.86 mg, 1.07 mmol) in 1,4-dioxane (10 mL) was added copper (I) iodide (203.24 mg, 1.07 mmol), potassium phosphate (2265.3 mg, 10.67 mmol), and 1H-pyrazole (363.26 mg, 5.34 mmol). The vial was sealed and heated in a microwave at 200° C. for 1 hour. The reaction mixture was diluted with water (50 mL) and EtOAc (30 mL), and the organics were separated, washed with brine (20 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography over silica (25 g, SNAP cartridge), eluting with a gradient of EtOAc:isohexane from 0% to 30%. Fractions containing desired product were combined and concentrated in vacuo to give 1-(3-benzyloxy-4-fluoro-phenyl)pyrazole (D71) (649.1 mg, 2.2984 mmol, 43.1% yield) as a pale orange oil; The vial was sealed the organics were separated washed with brine (20 mL) dried over MgSO4 filtered concentrated in vacuo The residue was purified by column chromatography over silica (25 g, SNAP cartridge) eluting with a gradient of EtOAc Fractions containing desired product concentrated in vacuo

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

Procedure: To a solution of 1-methyl-1H-pyrazole-5-boronic acid pinacol ester (1058.42 mg, 5.09 mmol) in MeCN (40 mL) and water (10 mL) was added 2-benzyloxy-4-bromo-1-fluoro-benzene [CAS: 1036724-54-5](1300 mg, 4.62 mmol), sodium carbonate (1470.8 mg, 13.88 mmol) and bis(triphenylphosphine)palladium (II) dichloride (164.24 mg, 0.2300 mmol). The reaction was then heated at 100° C. for 4 hours. The cooled reaction mixture was poured into EtOAc (70 mL) and water (100 mL). The organics were separated, and washed with brine (75 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was then purified over silica (25 g, SNAP cartridge), eluting with EtOAc in isohexane from 0% to 40%. Fractions containing desired product were combined and concentrated in vacuo to give 5-(3-benzyloxy-4-fluoro-phenyl)-1-methyl-pyrazole (D82) (1026.5 mg, 3.4543 mmol, 74.7% yield) as a colourless oil; The cooled reaction mixture The organics were separated washed with brine (75 mL) dried over MgSO4 filtered concentrated in vacuo The residue was then purified over silica (25 g, SNAP cartridge) eluting with EtOAc in isohexane from 0% to 40% Fractions containing desired product concentrated in vacuo

Conditions: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a microwave vial containing 2-benzyloxy-4-bromo-1-fluoro-benzene [CAS: 1036724-54-5](1500 mg, 5.34 mmol) and 3-methyl-1H-pyrazole (525.68 mg, 6.4 mmol) in 1,4-dioxane (10 mL) was added copper (I) iodide (101.62 mg, 0.5300 mmol), potassium phosphate (2265.26 mg, 10.67 mmol), and (1S,2S)-(+)-1,2-diaminocyclohexane (60.93 mg, 0.5300 mmol). The vial was sealed and heated in a microwave at 200° C. for 2 h 30 minutes. The reaction was diluted with water (50 mL) and EtOAc (30 mL), and the organics were separated, washed with brine (20 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography over silica (50 g, SNAP cartidge), eluting with a gradient of EtOAc:isohexane from 0% to 30%. Fractions containing the first eluting product were combined and concentrated in vacuo to give 1-(3-benzyloxy-4-fluoro-phenyl)-3-methyl-pyrazole (D66) (385 mg, 1.2274 mmol, 23% yield) as a colourless oil which crystallised on standing; The vial was sealed the organics were separated washed with brine (20 mL) dried over MgSO4 filtered concentrated in vacuo The residue was purified by column chromatography over silica (50 g, SNAP cartidge) eluting with a gradient of EtOAc Fractions containing the first eluting product concentrated in vacuo

Conditions: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a microwave vial containing 2-benzyloxy-4-bromo-1-fluoro-benzene [CAS: 1036724-54-5](1500 mg, 5.34 mmol) and 3-methyl-1H-pyrazole (525.68 mg, 6.4 mmol) in 1,4-dioxane (10 mL) was added copper (I) iodide (101.62 mg, 0.5300 mmol), potassium phosphate (2265.26 mg, 10.67 mmol), and (1S,2S)-(+)-1,2-diaminocyclohexane (60.93 mg, 0.5300 mmol). The vial was sealed and heated in a microwave at 200° C. for 2 h 30 minutes. The reaction was diluted with water (50 mL) and EtOAc (30 mL), and the organics were separated, washed with brine (20 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography over silica (50 g, SNAP cartidge), eluting with a gradient of EtOAc:isohexane from 0% to 30%. Fractions containing the first eluting product were combined and concentrated in vacuo to give 1-(3-benzyloxy-4-fluoro-phenyl)-3-methyl-pyrazole (D66) (385 mg, 1.2274 mmol, 23% yield) as a colourless oil which crystallised on standing; The vial was sealed the organics were separated washed with brine (20 mL) dried over MgSO4 filtered concentrated in vacuo The residue was purified by column chromatography over silica (50 g, SNAP cartidge) eluting with a gradient of EtOAc Fractions containing the first eluting product concentrated in vacuo

Conditions: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a microwave vial containing 2-benzyloxy-4-bromo-1-fluoro-benzene [CAS: 1036724-54-5](1500 mg, 5.34 mmol) and 3-methyl-1H-pyrazole (525.68 mg, 6.4 mmol) in 1,4-dioxane (10 mL) was added copper (I) iodide (101.62 mg, 0.5300 mmol), potassium phosphate (2265.26 mg, 10.67 mmol), and (1S,2S)-(+)-1,2-diaminocyclohexane (60.93 mg, 0.5300 mmol). The vial was sealed and heated in a microwave at 200° C. for 2 h 30 minutes. The reaction was diluted with water (50 mL) and EtOAc (30 mL), and the organics were separated, washed with brine (20 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography over silica (50 g, SNAP cartidge), eluting with a gradient of EtOAc:isohexane from 0% to 30%. Fractions containing the first eluting product were combined and concentrated in vacuo to give 1-(3-benzyloxy-4-fluoro-phenyl)-3-methyl-pyrazole (D66) (385 mg, 1.2274 mmol, 23% yield) as a colourless oil which crystallised on standing; The vial was sealed the organics were separated washed with brine (20 mL) dried over MgSO4 filtered concentrated in vacuo The residue was purified by column chromatography over silica (50 g, SNAP cartidge) eluting with a gradient of EtOAc Fractions containing the first eluting product concentrated in vacuo