1160653-94-0

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

Procedure: To a solution of 3-bromo-2-fluoro-6-methoxy-benzaldehyde (9.8 g, 42.06 mmol,) in dichloromethane (200 mL) at −50° C. was added a dichloromethane solution (1 M) of BBr3 (126 mL, 126 mmol) dropwise. The mixture was gradually warmed to room temperature and stirred for 1 h, then quenched with water. The mixture was extracted with dichloromethane three times. The organic layer were combined, washed with brine, dried over MgSO4, concentrated to give 3-bromo-2-fluoro-6-hydroxy-benzaldehyde as a off white solid (Yield: 9 g, 98%) quenched with water The mixture was extracted with dichloromethane three times washed with brine dried over MgSO4 concentrated

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

Procedure: To a solution of 4-bromo-3-fluoroanisole (10 g, 48.7 mmol, Matrix) in tetrahydrofuran (100 mL) at −78° C. was added lithium diisopropyl amine (32.5 mL, 1.8 M in THF, 58.4 mmol) dropwise during a period of 15 min. The mixture was stirred at −78° C. for another 20 mins. Then N,N-dimethyl-formamide (4.53 mL, 58.4 mmol) was added in one portion. The mixture was stirred at −78° C. for 10 min, then quenched with acetic acid (12 g, 194 mmol) and followed by the addition of water (61 mL). The mixture was partitioned between ethyl acetate and water. The organic layer was separated, concentrated. The residue was purified by chromatography (EtOAc:hexanes=1:4) to give 3-bromo-2-fluoro-6-methoxy-benzaldehyde as a yellow solid (Yield: 10 g, 89%) The mixture was stirred at −78° C. for 10 min The mixture was partitioned between ethyl acetate and water The organic layer was separated concentrated The residue was purified by chromatography (EtOAc:hexanes=1:4)

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

Procedure: To a solution of 4-bromo-3-fluoroanisole (10 g, 48.7 mmol, Matrix) in tetrahydrofuran (100 mL) at −78° C. was added lithium diisopropyl amine (32.5 mL, 1.8 M in THF, 58.4 mmol) dropwise during a period of 15 min. The mixture was stirred at −78° C. for another 20 mins. Then N,N-dimethyl-formamide (4.53 mL, 58.4 mmol) was added in one portion. The mixture was stirred at −78° C. for 10 min, then quenched with acetic acid (12 g, 194 mmol) and followed by the addition of water (61 mL). The mixture was partitioned between ethyl acetate and water. The organic layer was separated, concentrated. The residue was purified by chromatography (EtOAc:hexanes=1:4) to give 3-bromo-2-fluoro-6-methoxy-benzaldehyde as a yellow solid (Yield: 10 g, 89%) The mixture was stirred at −78° C. for 10 min The mixture was partitioned between ethyl acetate and water The organic layer was separated concentrated The residue was purified by chromatography (EtOAc:hexanes=1:4)

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

Procedure: To a solution of 3-bromo-2-fluoro-6-methoxy-benzaldehyde (9.8 g, 42.06 mmol,) in dichloromethane (200 mL) at −50° C. was added a dichloromethane solution (1 M) of BBr3 (126 mL, 126 mmol) dropwise. The mixture was gradually warmed to room temperature and stirred for 1 h, then quenched with water. The mixture was extracted with dichloromethane three times. The organic layer were combined, washed with brine, dried over MgSO4, concentrated to give 3-bromo-2-fluoro-6-hydroxy-benzaldehyde as a off white solid (Yield: 9 g, 98%) quenched with water The mixture was extracted with dichloromethane three times washed with brine dried over MgSO4 concentrated

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

Procedure: To a solution of 4-bromo-3-fluoroanisole (10 g, 48.7 mmol, Matrix) in tetrahydrofuran (100 mL) at −78° C. was added lithium diisopropyl amine (32.5 mL, 1.8 M in THF, 58.4 mmol) dropwise during a period of 15 min. The mixture was stirred at −78° C. for another 20 mins. Then N,N-dimethyl-formamide (4.53 mL, 58.4 mmol) was added in one portion. The mixture was stirred at −78° C. for 10 min, then quenched with acetic acid (12 g, 194 mmol) and followed by the addition of water (61 mL). The mixture was partitioned between ethyl acetate and water. The organic layer was separated, concentrated. The residue was purified by chromatography (EtOAc:hexanes=1:4) to give 3-bromo-2-fluoro-6-methoxy-benzaldehyde as a yellow solid (Yield: 10 g, 89%) The mixture was stirred at −78° C. for 10 min The mixture was partitioned between ethyl acetate and water The organic layer was separated concentrated The residue was purified by chromatography (EtOAc:hexanes=1:4)