4-bromo-2-chlorobenzaldehyde

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:

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5 g (22.78 mmol) of 4-bromo-2-chlorobenzaldehyde in 30 ml of tetrahydrofurane are successively added 3.47 g (28.47 mmol) of phenylboronic acid, 4.72 g (34.17 mmol) of potassium carbonate dissolved in 15 ml of water and 263 mg (0.01 equivalent) of tetrakis(triphenylphosphine) palladium. The reaction mixture is heated at 80° C. for 3 hrs. The reaction mixture is then cooled to ambient temperature and poured on 150 ml of brine. The watery layer is extracted three times with dichloromethane and the combined organic layers are successively washed by a 1M solution of sodium hydroxide, brine and filtered over a ChemElut cartridge to yield after concentration 4.6 g of a brown solid. Column chromatography (gradient heptane/chloroforme) yielded 3.29 g (65% yield) of 3-chlorobiphenyl-4-carbaldehyde as a white solid; mp=90-91° C. The reaction mixture is then cooled to ambient temperature The watery layer is extracted three times with dichloromethane the combined organic layers are successively washed by a 1M solution of sodium hydroxide, brine filtered over a ChemElut cartridge to yield after concentration 4.6 g of a brown solid

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-bromo-2-chlorobenzonitrile (2.0 g, 9.2 mmol) in toluene (50 mL) at −78° C. under argon was added DIBAL (1M solution in toluene, 13.9 mL, 13.9 mmol). The mixture was allowed to warm to −50° C. over 4 h. MeOH (4.5 mL) and water (4.5 mL) were added and the mixture stirred for 10 min at −50° C. The mixture was allowed to warm to rt, acidified with 2N HCl (pH<7) and extracted with EtOAc (200 mL) and water (100 mL). The aqueous was further extracted with EtOAc (2×50 mL), the combined organics were then washed with brine and dried (MgSO4). The solvent was removed in vacuo and the residue purified by column chromatography (25% DCM: Iso-hexane) to give 4-bromo-2-chlorobenzaldehyde. To a solution of 4-bromo-2-chlorobenzaldehyde (750 mg, 3.4 mmol) in DME (22 mL) and EtOH (15 mL) was added 3-carboxamidobenzene boronic acid (676 mg, 4.1 mmol) and 2M Na2CO3 solution (15 mL). Argon was bubbled through the mixture for 15 min. Bis(triphenylphosphino) palladium dichloride (120 mg, 0.17 mmol) was added and the reaction heated to 75° C. for 6.5 h before cooling to rt. The mixture was partitioned between water (200 mL) and EtOAc (200 mL), the aqueous was extracted with EtOAc (2×50 mL) and the combined organics dried (MgSO4). The solvent was removed in vacuo and the residue purified by column chromatography (50% EtOAc: Iso-hexane to 100% EtOAc) to give the title compound: RT=3.19 min; m/z (ES+)=301.0 [M+H+MeCN]+. to warm to rt extracted with EtOAc (200 mL) and water (100 mL) The aqueous was further extracted with EtOAc (2×50 mL) the combined organics were then washed with brine dried (MgSO4) The solvent was removed in vacuo the residue purified by column chromatography (25% DCM: Iso-hexane)

Conditions: temp:37.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 4-bromo-2-chlorobenzaldehyde (1150 mg, 5240 μmol), (r)-(+)-2-methyl-2-propanesulfinamide (1588 mg, 13100 μmol), copper(ii) sulfate (696.4 μl, 15720 μmol) in DCM (10 mL) was stirred at 37° C. for 78 h. Reaction filtered through Celite, and solid washed repeatedly with DCM. Filtrate concentrated then purified on silica (80 g) eluting product with 0>30% of EtOAc/Hex. MS (ESI pos. ion) m/z: 322/324 (MH+). Calc'd exact mass for C11H13BrClNOS: 321/323. Reaction filtered through Celite, and solid washed repeatedly with DCM Filtrate concentrated then purified on silica (80 g) eluting product with 0>30% of EtOAc/Hex

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

Procedure: To a stirring solution of (4-bromo-2-chlorophenyl)methanol (4.5 g, 20 mmol) in DCM (50 mL) was added Dess-Martin periodinane (9.3 g) at 23° C. Reaction refluxed after addition. After 20 min, TLC (1:4 EtOAc/Hex) suggests full conversion of alcohol. Suspension then washed with 5% NaHCO3 (100 mL plus 15 g dry NaHCO3). Organic dried over MgSO4, concentrated onto dry silica (15 g), then purified on silica (120 g) eluting with 0>10% EtOAc/hex. 4-bromo-2-chlorobenzaldehyde isolated as a white solid. Reaction refluxed after addition Suspension then washed with 5% NaHCO3 (100 mL plus 15 g dry NaHCO3) Organic dried over MgSO4 concentrated onto dry silica (15 g) purified on silica (120 g) eluting with 0>10% EtOAc/hex

Conditions: temp:37.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 4-bromo-2-chlorobenzaldehyde (1150 mg, 5240 μmol), (r)-(+)-2-methyl-2-propanesulfinamide (1588 mg, 13100 μmol), copper(ii) sulfate (696.4 μl, 15720 μmol) in DCM (10 mL) was stirred at 37° C. for 78 h. Reaction filtered through Celite, and solid washed repeatedly with DCM. Filtrate concentrated then purified on silica (80 g) eluting product with 0>30% of EtOAc/Hex. MS (ESI pos. ion) m/z: 322/324 (MH+). Calc'd exact mass for C11H13BrClNOS: 321/323. Reaction filtered through Celite, and solid washed repeatedly with DCM Filtrate concentrated then purified on silica (80 g) eluting product with 0>30% of EtOAc/Hex

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

Procedure: To a stirring solution of (4-bromo-2-chlorophenyl)methanol (4.5 g, 20 mmol) in DCM (50 mL) was added Dess-Martin periodinane (9.3 g) at 23° C. Reaction refluxed after addition. After 20 min, TLC (1:4 EtOAc/Hex) suggests full conversion of alcohol. Suspension then washed with 5% NaHCO3 (100 mL plus 15 g dry NaHCO3). Organic dried over MgSO4, concentrated onto dry silica (15 g), then purified on silica (120 g) eluting with 0>10% EtOAc/hex. 4-bromo-2-chlorobenzaldehyde isolated as a white solid. Reaction refluxed after addition Suspension then washed with 5% NaHCO3 (100 mL plus 15 g dry NaHCO3) Organic dried over MgSO4 concentrated onto dry silica (15 g) purified on silica (120 g) eluting with 0>10% EtOAc/hex

Conditions: temp:37.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 4-bromo-2-chlorobenzaldehyde (1150 mg, 5240 μmol), (r)-(+)-2-methyl-2-propanesulfinamide (1588 mg, 13100 μmol), copper(ii) sulfate (696.4 μl, 15720 μmol) in DCM (10 mL) was stirred at 37° C. for 78 h. Reaction filtered through Celite, and solid washed repeatedly with DCM. Filtrate concentrated then purified on silica (80 g) eluting product with 0>30% of EtOAc/Hex. MS (ESI pos. ion) m/z: 322/324 (MH+). Calc'd exact mass for C11H13BrClNOS: 321/323. Reaction filtered through Celite, and solid washed repeatedly with DCM Filtrate concentrated then purified on silica (80 g) eluting product with 0>30% of EtOAc/Hex