4-bromo-3-fluorobenzaldehyde

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: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:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-bromo-3-fluorobenzaldehyde (100 mg, 0.5 mmol), 1,2-diphenylethanone (118 mg, 0.6 mmol) and urea (90 mg, 1.5 mmol) in ethanol (3 mL) was added conc. HCL (0.1 mL). The mixture was refluxed under N2 atmosphere for 6 hrs. Solvent was removed; purified by silica gel column chromatography (PE:EtOAc=10:1 to PE:EtOAc=1:1) to give product (130 mg, yield 62%). 1H NMR (DMSO-d6 400 MHz): δ 8.74 (s, 1H), 7.74-7.68 (m, 1H), 7.54 (s, 1H), 7.26-7.15 (m, 7H), 7.03-6.95 (m, 3H), 6.81-6.79 (m, 2H), 5.24 (d, J=2.8 Hz, 1H). was added conc. HCL (0.1 mL) The mixture was refluxed under N2 atmosphere for 6 hrs Solvent was removed purified by silica gel column chromatography (PE:EtOAc=10:1 to PE:EtOAc=1:1)

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

Procedure: 4-Bromo-3-fluorobenzaldehyde (as described in Example 18, Step A) (3.61 g, 17.7 mmol) was dissolved in anhydrous diethyl ether (40 mL). To this solution was added a 1.0M solution of 4-chlorophenyl-magnesium bromide (21.3 mL, 21.3 mmol). After stirring at ambient temperature for 4 hr the reaction was quenched with satd. NH4Cl and extracted with Et2O. The organic layer was washed with satd NaHCO3 solution, water, brine, dried (MgSO4), concentrated and purified by chromatography (SiO2, 10% EtOAc/hexane) to give the title compound. was quenched with satd NH4Cl and extracted with Et2O The organic layer was washed with satd NaHCO3 solution, water, brine dried (MgSO4) concentrated purified by chromatography (SiO2, 10% EtOAc/hexane)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-3-fluorobenzaldehyde (1.6 g, 7.88 mmol) in diethylether (20 mL) at 0° C. was added 4-chlorophenyl-magnesiumbromide (1Mether, 9.46 mL, 9.46 mmol) dropwise via syringe. The cooling bath was removed and after the mixture was stirred for 18 hr it was cooled to 0° C. and saturated NH4Cl solution (20 mL) was added to quench the reaction. The reaction mixture was partitioned between EtOAc and saturated NaHCO3 solution. The EtOAc layer was washed with H2O, brine, and dried (MgSO4). Filtration and concentration in vacuo gave the title compound as a solid after chromatography (silica gel, hexane:EtOAc/85:15). The cooling bath was removed saturated NH4Cl solution (20 mL) was added to quench the reaction The reaction mixture was partitioned between EtOAc and saturated NaHCO3 solution The EtOAc layer was washed with H2O, brine dried (MgSO4) Filtration and concentration in vacuo

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

Procedure: To a well-stirred mixture of 4-bromo-3-fluorobenzyl alcohol (as described in Example 9, Step B) (10.25 g, 0.05 mol), TEMPO (0.781 g, 0.005 mol) and tetrabutylammonium fluoride (1.39 g, 0.005 mol) in CH2Cl2 (200 mL) and a solution of 0.5M NaHCO3/0.05M K2CO3 (200 mL) was added N-chlorosuccinimide (9.35 g, 0.07 mol). After 6 hrs, the layers were separated, the aqueous layer back-washed with CH2Cl2 (2×50 mL), the organics combined and dried (Na2SO4). The solution was filtered, concentrated to half its volume, then chromatographed (silica gel, CH2Cl2) to give the title compound. the layers were separated the aqueous layer back-washed with CH2Cl2 (2×50 mL) dried (Na2SO4) The solution was filtered concentrated to half its volume chromatographed (silica gel, CH2Cl2)