2-bromo-4-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:; See reaction.notes.procedure_details.

Procedure: 2-bromo-4-fluorobenzaldehyde (800 mg, 3.9 mmol), methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinate (1.2 g, 4.7 mmol), Pd(dppf)Cl2 (433 mg, 0.6 mmol), and K2CO3 (1.1 g, 7.9 mmol) were dissolved in 1,4-dioxane (40 mL) and water (10 mL) and the resulting mixture was heated to 65° C. After 1.5 h the resulting mixture was cooled to room temperature, diluted with EtOAc, washed with water and brine, dried (Na2SO4), and dry packed onto silica gel. Column chromatography yielded the title compound. washed with water and brine dried (Na2SO4) dry

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-bromo-4-fluoro-benzaldehyde (30.0 g, 148 mmol), Na2CO3 (78.31 g, 738.8 mmol) and 2-benzyloxy propanol (24.56 g, 147.8 mmol) in anhydrous DMSO (300 mL) was heated with stirring at 130° C. (bath temp) for 72 h under N2. The reaction mixture was cooled to rt and diluted with H2O and extracted with EtOAc. The organic layer was washed with H2O then brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by flash chromatography (hexane to 30% EtOAc in hexane) to give the title compound: yield 3.84 g (7%). was heated The reaction mixture was cooled to rt extracted with EtOAc The organic layer was washed with H2O brine, dried (MgSO4) concentrated in vacuo The residue was purified by flash chromatography (hexane to 30% EtOAc in hexane)

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-bromo-4-fluoro-benzaldehyde (32.0 g, 157 mmol), Na2CO3 (85.5 g, 788 mmol), and 2-benzyloxy ethanol (24.0 g, 158 mmol) in anhydrous DMSO (300 mL) were heated under N2 at 130° C. (bath temp) for 18 h. The reaction mixture cooled to rt, diluted with H2O (100 mL), and extracted with EtOAc The organic layer was washed with H2O then brine, dried (MgSO4), and concentrated in vacuo The residue was purified by flash chromatography (hexane to 10% EtOAc in hexane) to give the title compound as a viscous liquid: yield 11.8 g (22%). The reaction mixture cooled to rt extracted with EtOAc The organic layer was washed with H2O brine, dried (MgSO4) concentrated in vacuo The residue was purified by flash chromatography (hexane to 10% EtOAc in hexane)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromo-4-fluorobenzaldehyde (300 mg, 1.48 mmol) in 3.0 mL of N,N-dimethylformamide was added potassium carbonate (204 mg, 1.48 mmol), piperidine (154 μL, 1.55 mmol) at room temperature. After being stirred at 110° C. overnight, the reaction mixture was diluted with a 2:1 solution of ethyl acetate and hexane. The solution was washed with water, brine, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=100/0 to 75/25) to obtain the title compound (355 mg, 90%). The solution was washed with water, brine dried over MgSO4 After filtration the filtrate was concentrated in vacuo the residue was purified by silica gel column chromatography (hexane/ethyl acetate=100/0 to 75/25)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromo-4-fluorobenzaldehyde (300 mg, 1.48 mmol) in 3.0 mL of N,N-dimethylformamide was added potassium carbonate (204 mg, 1.48 mmol), piperidine (154 μL, 1.55 mmol) at room temperature. After being stirred at 110° C. overnight, the reaction mixture was diluted with a 2:1 solution of ethyl acetate and hexane. The solution was washed with water, brine, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=100/0 to 75/25) to obtain the title compound (355 mg, 90%). The solution was washed with water, brine dried over MgSO4 After filtration the filtrate was concentrated in vacuo the residue was purified by silica gel column chromatography (hexane/ethyl acetate=100/0 to 75/25)

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

Procedure: 2-Bromo-4-fluorotoluene (10.215 g) was dissolved in ethyl acetate (100 ml), N-bromosuccinimide (11.3 g) and 70% benzoyl peroxide (200 mg) were added thereto, and the resulting mixture was stirred under heating at 80° C. for 1 hr. After the reaction solution was cooled, the resulting insoluble matters were filtered off. The resulting filtrate was washed with an aqueous solution of saturated sodium bicarbonate, dried (over MgSO4) and evaporated. The resulting residue was dissolved in acetic acid (30 ml), water (30 ml) and hexamethylene tetramine (15.141 g) were added thereto, and the resulting mixture was heated under stirring at 100° C. for 1 hr. To the mixture was added 38% hydrochloric acid (20 ml), which was then stirred for 1 hr, and then it was cooled as it was, and extracted with ethyl acetate. The resulting organic phase was washed with an aqueous solution of saturated sodium bicarbonate, dried (over MgSO4) and evaporated. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane system), to give the title compound as a colorless solid (4.376 g, yield; 41%). After the reaction solution was cooled the resulting insoluble matters were filtered off The resulting filtrate was washed with an aqueous solution of saturated sodium bicarbonate dried (over MgSO4) evaporated The resulting residue was dissolved in acetic acid (30 ml) water (30 ml) and hexamethylene tetramine (15.141 g) were added the resulting mixture was heated under stirring at 100° C. for 1 hr To the mixture was added 38% hydrochloric acid (20 ml), which was then stirred for 1 hr it was cooled as it extracted with ethyl acetate The resulting organic phase was washed with an aqueous solution of saturated sodium bicarbonate dried (over MgSO4) evaporated The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane system)

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

Procedure: 2-Bromo-4-fluorotoluene (10.215 g) was dissolved in ethyl acetate (100 ml), N-bromosuccinimide (11.3 g) and 70% benzoyl peroxide (200 mg) were added thereto, and the resulting mixture was stirred under heating at 80° C. for 1 hr. After the reaction solution was cooled, the resulting insoluble matters were filtered off. The resulting filtrate was washed with an aqueous solution of saturated sodium bicarbonate, dried (over MgSO4) and evaporated. The resulting residue was dissolved in acetic acid (30 ml), water (30 ml) and hexamethylene tetramine (15.141 g) were added thereto, and the resulting mixture was heated under stirring at 100° C. for 1 hr. To the mixture was added 38% hydrochloric acid (20 ml), which was then stirred for 1 hr, and then it was cooled as it was, and extracted with ethyl acetate. The resulting organic phase was washed with an aqueous solution of saturated sodium bicarbonate, dried (over MgSO4) and evaporated. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane system), to give the title compound as a colorless solid (4.376 g, yield; 41%). After the reaction solution was cooled the resulting insoluble matters were filtered off The resulting filtrate was washed with an aqueous solution of saturated sodium bicarbonate dried (over MgSO4) evaporated The resulting residue was dissolved in acetic acid (30 ml) water (30 ml) and hexamethylene tetramine (15.141 g) were added the resulting mixture was heated under stirring at 100° C. for 1 hr To the mixture was added 38% hydrochloric acid (20 ml), which was then stirred for 1 hr it was cooled as it extracted with ethyl acetate The resulting organic phase was washed with an aqueous solution of saturated sodium bicarbonate dried (over MgSO4) evaporated The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane system)