1-(5-bromo-2-fluorophenyl)ethanol

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:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Compound 4b (50.0g, 228 mmol) along with 300 ml dichloromethane was charged into 2 liter round bottom flask. Crushed pyridinum dichromate (171.0 g, 456 mmol) and powdered molecular sieves (10 g) were both added into the flask. The heterogeneous reaction mixture was stirred for 16 hours at 20° C. The resulting reaction mixture was filtered through celite and washed with ether (500 ml×3). The combined filtrate was concentrated under reduced pressure. The crude product was eluted through a short silica gel pad (3 inches in length) withlo% EtOAc in hexane. The resulting product (42.0 g, yield=84%) was used for the following step. both added into the flask The resulting reaction mixture was filtered through celite washed with ether (500 ml×3) The combined filtrate was concentrated under reduced pressure The crude product was eluted through a short silica gel pad (3 inches in length) withlo% EtOAc in hexane

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Compound 4b (50.0 g, 228 mmol) along with 300 ml dichloromethane was charged into 2 liter round bottom flask. Crushed pyridinum dichromate (171.0 g, 456 mmol) and powdered molecular sieves (10 g) were both added into the flask. The heterogeneous reaction mixture was stirred for 16 hours at 20° C. The resulting reaction mixture was filtered through celite and washed with ether (500 ml×3). The combined filtrate was concentrated under reduced pressure. The crude product was eluted through a short silica gel pad (3 inches in length) with 10% EtOAc in hexane. The resulting product (42.0 g, yield=84%) was used for the following step. both added into the flask The resulting reaction mixture was filtered through celite washed with ether (500 ml×3) The combined filtrate was concentrated under reduced pressure The crude product was eluted through a short silica gel pad (3 inches in length) with 10% EtOAc in hexane

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

Procedure: To a solution of 1-(5-Bromo-2-fluoro-phenyl)-ethanol 102 (105 g, 0.479 mol) in dioxane (2 L) was added manganese dioxide (203 g, 2.35 mol). The reaction mixture was heated under reflux for 5 hours. The reaction mixture was allowed to cool to room temperature. The reaction mixture was filtered through Celite and the solid was washed with ether (1 L). The combined filtrate was evaporated under reduced pressure to afford the 1-(5-Bromo-2-fluoro-phenyl)-ethanone 103 (95.7 g, 0.441 mol) which was used in the next step without further purification. The reaction mixture was heated under reflux for 5 hours The reaction mixture was filtered through Celite the solid was washed with ether (1 L) The combined filtrate was evaporated under reduced pressure

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

Procedure: To a solution of 5-bromo-2-fluorobenzaldehyde 101 (100 g, 0.492 mol) in ether (500 mL), cooled in an ice bath, was added a 3 M solution of methyl magnesium bromide in ether (173 mL, 0.516 mol) in a dropwise manner. The reaction mixture was stirred for 30 minutes in the ice bath. The reaction mixture was allowed to warm to room temperature and was stirred for 15 minutes. The reaction mixture was cooled in an ice bath and the reaction was quenched by addition of water in a dropwise manner. The reaction mixture was acidified with dilute hydrochloric acid. The organic layer was separated. The aqueous layer was extracted with ether for two times. The combined organic layer was dried over magnesium sulfate and evaporated under reduced pressure to afford 1-(5-Bromo-2-fluoro-phenyl)-ethanol 102 (106 g, 0.484 mol) which was used in the next step without further purification. The reaction mixture was cooled in an ice bath the reaction was quenched by addition of water in a dropwise manner The organic layer was separated The aqueous layer was extracted with ether for two times The combined organic layer was dried over magnesium sulfate evaporated under reduced pressure

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

Procedure: To a solution of 5-bromo-2-fluorobenzaldehyde 101 (100 g, 0.492 mol) in ether (500 mL), cooled in an ice bath, was added a 3 M solution of methyl magnesium bromide in ether (173 mL, 0.516 mol) in a dropwise manner. The reaction mixture was stirred for 30 minutes in the ice bath. The reaction mixture was allowed to warm to room temperature and was stirred for 15 minutes. The reaction mixture was cooled in an ice bath and the reaction was quenched by addition of water in a dropwise manner. The reaction mixture was acidified with dilute hydrochloric acid. The organic layer was separated. The aqueous layer was extracted with ether for two times. The combined organic layer was dried over magnesium sulfate and evaporated under reduced pressure to afford 1-(5-Bromo-2-fluoro-phenyl)-ethanol 102 (106 g, 0.484 mol) which was used in the next step without further purification. The reaction mixture was cooled in an ice bath the reaction was quenched by addition of water in a dropwise manner The organic layer was separated The aqueous layer was extracted with ether for two times The combined organic layer was dried over magnesium sulfate evaporated under reduced pressure

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

Procedure: To a solution of 1-(5-bromo-2-fluoro-phenyl)-ethanol 102 (105 g, 0.479 mol.) in dioxane (2 L) was added manganese dioxide (203 g, 2.35 mol.). The reaction mixture was heated under reflux for 5 hours. The reaction mixture was allowed to cool to room temperature. The reaction mixture was filtered through Celite (i.e., diatomaceous earth) and the solid was washed with ether (1 L). The combined filtrate was evaporated under reduced pressure to afford the 1-(5-bromo-2-fluoro-phenyl)-ethanone 103 (95.7 g, 0.441 mol.) which was used in the next step without further purification. The reaction mixture was heated under reflux for 5 hours The reaction mixture was filtered through Celite (i.e., diatomaceous earth) the solid was washed with ether (1 L) The combined filtrate was evaporated under reduced pressure

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

Procedure: To a solution of 5-bromo-2-fluorobenzaldehyde 101 (100 g, 0.492 mol.) in ether (500 mL), cooled in an ice bath, was added a 3 M solution of methyl magnesium bromide in ether (i.e., diethyl ether) (173 mL, 0.516 mol.) in a dropwise manner. The reaction mixture was stirred for 30 minutes in the ice bath. The reaction mixture was allowed to warm to room temperature and was stirred for 15 minutes. The reaction mixture was cooled in an ice bath and the reaction was quenched by addition of water in a dropwise manner. The reaction mixture was acidified with dilute hydrochloric acid. The organic layer was separated. The aqueous layer was extracted with ether for two times. The combined organic layer was dried over magnesium sulfate and evaporated under reduced pressure to afford 1-(5-bromo-2-fluoro-phenyl)-ethanol 102 (106 g, 0.484 mol.) which was used in the next step without further purification. The reaction mixture was cooled in an ice bath the reaction was quenched by addition of water in a dropwise manner The organic layer was separated The aqueous layer was extracted with ether for two times The combined organic layer was dried over magnesium sulfate evaporated under reduced pressure

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Compound 4b (50.0 g, 228 mmol) along with 300 ml dichloromethane was charged into 2 liter round bottom flask. Crushed pyridinium dichromate (171.0 g, 456 mmol) and powdered molecular sieves (10 g) were both added into the flask. The heterogeneous reaction mixture was stirred for 16 hours at 20° C. The resulting reaction mixture was filtered through celite and washed with ether (500 ml×3). The combined filtrate was concentrated under reduced pressure. The crude product was eluted through a short silica gel pad (3 inches in length) with 10% EtOAc in hexane. The resulting product (42.0 g, yield=84%) was used for the following step. both added into the flask The resulting reaction mixture was filtered through celite washed with ether (500 ml×3) The combined filtrate was concentrated under reduced pressure The crude product was eluted through a short silica gel pad (3 inches in length) with 10% EtOAc in hexane