5-bromo-2-chloro-4-hydroxybenzonitrile

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: A mixture of compound 37 (20.5 g, 88.1 mmol), allyl bromide (11.2 mL, 132 mmol) and K2CO3 (24.4 g, 176 mmol) in acetone (440 mL) was stirred for 3 hours under reflux. The mixture was filtrated and concentrated in vacuo. The resultant was partitioned between EtOAc and water. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography to afford the product 38 (15.6 g, 65%) as a white solid. under reflux The mixture was filtrated concentrated in vacuo The resultant was partitioned between EtOAc and water The organic layer was washed with brine dried over MgSO4 filtered concentrated in vacuo The residue was purified by silica gel column chromatography

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

Procedure: A mixture of compound 37 (20.5 g, 88.1 mmol), allyl bromide (11.2 mL, 132 mmol) and K2CO3 (24.4 g, 176 mmol) in acetone (440 mL) was stirred for 3 hours under reflux. The mixture was filtrated and concentrated in vacuo. The resultant was partitioned between EtOAc and water. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography to afford the product 38 (15.6 g, 65%) as a white solid. under reflux The mixture was filtrated concentrated in vacuo The resultant was partitioned between EtOAc and water The organic layer was washed with brine dried over MgSO4 filtered concentrated in vacuo The residue was purified by silica gel column chromatography

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

Procedure: To a solution of 2-chloro-4-hydroxybenzonitrile (10 g, 65.1 mmol) in CH3CN (200 mL) was added CF3SO3H (6.33 g, 71.6 mmol) and NBS (16.2 g, 94.1 mmol) at −30° C. After being stirred for 18 hours at room temperature, the mixture was quenched with aq. saturated NaHSO4 solution and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography to afford the product 37 (10.5 g, 66%) as a white solid. the mixture was quenched with aq. saturated NaHSO4 solution extracted with EtOAc The organic layer was washed with brine dried over MgSO4 filtered concentrated in vacuo The residue was purified by silica gel column chromatography

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

Procedure: A mixture of 5-bromo-2-chloro-4-hyroxybenzonitrile (compound 87, 38.1 g, 164 mmol), dimethyl sulfate (20.1 mL, 213 mmol), and lithium hydroxide monohydrate (8.93 g, 213 mmol) in THF (500 mL) was refluxed overnight. The mixture was cooled to ambient temperature and then diluted with EtOAc. The EtOAc solution was washed with water and brine prior to drying over anhydrous MgSO4. Filtration and removal of the voletiles under reduced pressure left the crude product which was purified by column chromatography (5-40% EtOAC/hexanes) to yield 5-bromo-2-chloro-4-methoxybenzonitrile (30.7 g, 76%) as a white solid. was refluxed overnight The EtOAc solution was washed with water and brine to drying over anhydrous MgSO4 Filtration and removal of the voletiles under reduced pressure left the crude product which was purified by column chromatography (5-40% EtOAC/hexanes)

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

Procedure: To a solution of 2-chloro-4-hydroxybenzonitrile (compound 86, 10.0 g, 65.1 mmol) in acetonitrile (200 mL) was added triflic acid (10.0 mL, 71.6 mmol) and NBS (16.2 g, 91.2 mmol) at −30° C. The solution was allowed to warm up to room temperature and stirred overnight prior to quenching with saturated sodium bisulfite. The mixture was diluted with water and extracted with EtOAc. The organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude residue was purified by column chromatography (5-40% EtOAc/hexanes) to yield title compound (9.80 g, 65%) as a white solid. to quenching with saturated sodium bisulfite The mixture was diluted with water extracted with EtOAc The organic layer was dried over anhydrous MgSO4 filtered concentrated in vacuo The crude residue was purified by column chromatography (5-40% EtOAc/hexanes)

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

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

Procedure: A mixture of 5-bromo-2-chloro-4-hyroxybenzonitrile (compound 87, 38.1 g, 164 mmol), dimethyl sulfate (20.1 mL, 213 mmol), and lithium hydroxide monohydrate (8.93 g, 213 mmol) in THF (500 mL) was refluxed overnight. The mixture was cooled to ambient temperature and then diluted with EtOAc. The EtOAc solution was washed with water and brine prior to drying over anhydrous MgSO4. Filtration and removal of the voletiles under reduced pressure left the crude product which was purified by column chromatography (5-40% EtOAC/hexanes) to yield 5-bromo-2-chloro-4-methoxybenzonitrile (30.7 g, 76%) as a white solid. was refluxed overnight The EtOAc solution was washed with water and brine to drying over anhydrous MgSO4 Filtration and removal of the voletiles under reduced pressure left the crude product which was purified by column chromatography (5-40% EtOAC/hexanes)

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

Procedure: To a solution of 2-chloro-4-hydroxybenzonitrile (compound 86, 10.0 g, 65.1 mmol) in acetonitrile (200 mL) was added triflic acid (10.0 mL, 71.6 mmol) and NBS (16.2 g, 91.2 mmol) at −30° C. The solution was allowed to warm up to room temperature and stirred overnight prior to quenching with saturated sodium bisulfite. The mixture was diluted with water and extracted with EtOAc. The organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude residue was purified by column chromatography (5-40% EtOAc/hexanes) to yield title compound (9.80 g, 65%) as a white solid. to quenching with saturated sodium bisulfite The mixture was diluted with water extracted with EtOAc The organic layer was dried over anhydrous MgSO4 filtered concentrated in vacuo The crude residue was purified by column chromatography (5-40% EtOAc/hexanes)

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

Procedure: A mixture of compound 37 (20.5 g, 88.1 mmol), allyl bromide (11.2 mL, 132 mmol) and K2CO3 (24.4 g, 176 mmol) in acetone (440 mL) was stirred for 3 hours under reflux. The mixture was filtrated and concentrated in vacuo. The resultant was partitioned between EtOAc and water. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography to afford the product 38 (15.6 g, 65%) as a white solid. under reflux The mixture was filtrated concentrated in vacuo The resultant was partitioned between EtOAc and water The organic layer was washed with brine dried over MgSO4 filtered concentrated in vacuo The residue was purified by silica gel column chromatography

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

Procedure: A mixture of compound 37 (20.5 g, 88.1 mmol), allyl bromide (11.2 mL, 132 mmol) and K2CO3 (24.4 g, 176 mmol) in acetone (440 mL) was stirred for 3 hours under reflux. The mixture was filtrated and concentrated in vacuo. The resultant was partitioned between EtOAc and water. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography to afford the product 38 (15.6 g, 65%) as a white solid. under reflux The mixture was filtrated concentrated in vacuo The resultant was partitioned between EtOAc and water The organic layer was washed with brine dried over MgSO4 filtered concentrated in vacuo The residue was purified by silica gel column chromatography