4-fluoro-2-(trifluoromethyl)benzaldehyde

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: The 2-trifluoromethyl-4-fluorobenzaldehyde (48.4 g, 252 mmol) was converted to product in a manner substantially analogous to Preparation 59 to yield 50.1 g. (84%). EA, MS(FD). to yield 50.1 g

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

Procedure: The 2-trifluoromethyl-4-fluorobenzaldehyde (48.4 g, 252 mmol) was converted to product in a manner substantially analogous to Preparation 59 to yield 50.1 g. (84%). EA, MS(FD). to yield 50.1 g

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

Procedure: In analogy to Example 214, step 1, 5-[2-(2-chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1-methyl-1H-pyridin-2-one(Example 151, step 7) was reacted with 4-fluoro-2-(trifluoromethyl)benzaldehyde in the presence of cesium carbonate to give the title compound as a colorless oil. MS (m/e, ISP neg. ion)=532.0 [M−H+].

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

Procedure: In analogy to Example 214, step 1, 5-[2-(2-chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1-methyl-1H-pyridin-2-one(Example 151, step 7) was reacted with 4-fluoro-2-(trifluoromethyl)benzaldehyde in the presence of cesium carbonate to give the title compound as a colorless oil. MS (m/e, ISP neg. ion)=532.0 [M−H+].

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

Procedure: To a stirred solution of 5-[2-(2-chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1,3-dimethyl-1H-pyridin-2-one (Example 203, step 5, 80 mg) in N,N-dimethylacetamide (1.5 ml) were added 4-fluoro-2-(trifluormethyl)benzaldehyde (63 mg) and cesium carbonate (208 mg). The mixture was stirred at room temperature for 3 h. Water was added and the mixture was extracted with ethyl acetate. The organic phase was dried (MgSO4), filtered and concentrated. The product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>0:1) to give the title compound (111 mg) as an off-white solid. MS (m/e)=548.2 [M+H+]. the mixture was extracted with ethyl acetate The organic phase was dried (MgSO4) filtered concentrated The product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>0:1)

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

Procedure: To a stirred solution of 5-[2-(2-chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1,3-dimethyl-1H-pyridin-2-one (Example 203, step 5, 80 mg) in N,N-dimethylacetamide (1.5 ml) were added 4-fluoro-2-(trifluormethyl)benzaldehyde (63 mg) and cesium carbonate (208 mg). The mixture was stirred at room temperature for 3 h. Water was added and the mixture was extracted with ethyl acetate. The organic phase was dried (MgSO4), filtered and concentrated. The product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>0:1) to give the title compound (111 mg) as an off-white solid. MS (m/e)=548.2 [M+H+]. the mixture was extracted with ethyl acetate The organic phase was dried (MgSO4) filtered concentrated The product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>0:1)

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

Procedure: A suspension of 4-fluoro-2-trifluoromethylbenzaldehyde (500 mg, 2.60 mmol), dimethylamine (5.5 mol/L in ethanol, 0.95 mL, 5.2 mmol), potassium carbonate (360 mg, 2.6 mmol) in 5.2 mL of N,N-dimethylformamide was stirred at 110° C. overnight in a sealed tube. After the reaction mixture was diluted with water, the solution was extracted with ether. The extract was washed with 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=85/15 to 75/25) to obtain the title compound as a pale yellow powder (393 mg, 70%). the solution was extracted with ether The extract was washed with brine dried over MgSO4 After filtration the filtrate was concentrated in vacuo the residue was purified by silica gel column chromatography (hexane/ethyl acetate=85/15 to 75/25)

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

Procedure: A suspension of 4-fluoro-2-trifluoromethylbenzaldehyde (500 mg, 2.60 mmol), dimethylamine (5.5 mol/L in ethanol, 0.95 mL, 5.2 mmol), potassium carbonate (360 mg, 2.6 mmol) in 5.2 mL of N,N-dimethylformamide was stirred at 110° C. overnight in a sealed tube. After the reaction mixture was diluted with water, the solution was extracted with ether. The extract was washed with 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=85/15 to 75/25) to obtain the title compound as a pale yellow powder (393 mg, 70%). the solution was extracted with ether The extract was washed with brine dried over MgSO4 After filtration the filtrate was concentrated in vacuo the residue was purified by silica gel column chromatography (hexane/ethyl acetate=85/15 to 75/25)

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

Procedure: Sodium hydride (343.2 mg, 8.58 mmol, 60% dispersed oil) was slowly added to cyclohexaneethanol (1 g, 7.8 mmol) dissolved in 30 ml of dried dimethylformamide under nitrogen at room temperature while stirring. The mixture was further stirred at room temperature for 30 minutes. Then, 4-fluoro-2-(trifluoromethyl)benzaldehyde (1.2 g, 7.8 mmol) dissolved in dried dimethylformamide was added thereto over 10 minutes and stirred at room temperature for 18 hours until the initial product disappeared. Subsequently, ice water was added thereto, and the resulting mixture was extracted with ethyl acetate and water. The organic layer was washed with water several times, dried with anhydrous magnesium sulfate, filtered and solvent-evaporated. The residual oil was chromatographed on the silica gel column (hexane:ethyl acetate-20:1) to afford the intermediate, 4-(2-cyclohexylethoxy)-2-(trifluoromethyl)benzaldehyde (1.77 g, yield: 75.6%). The mixture was further stirred at room temperature for 30 minutes was added the resulting mixture was extracted with ethyl acetate and water The organic layer was washed with water several times dried with anhydrous magnesium sulfate filtered solvent-evaporated The residual oil was chromatographed on the silica gel column (hexane:ethyl acetate-20:1)

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

Procedure: The 2-trifluoromethyl-4-fluorobenzaldehyde (48.4 g, 252 mmol) was converted to product in a manner substantially analogous to Preparation 59 to yield 50.1 g. (84%). EA, MS(FD). to yield 50.1 g