2-(difluoromethyl)benzaldehyde

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: After dissolving 1-bromo-2-difluoromethylbenzene (3.23 g) in tetrahydrofuran (65 ml), the mixture was cooled to −78° C. After then adding n-butyllithium (2.64 M solution in hexane, 6.5 ml) and stirring for 30 minutes, N,N-dimethylformamide (2.4 ml) was added and stirring was continued for 3 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and then the mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and brine in that order and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (991 mg). extracted with ethyl acetate The organic layer was washed with water and brine in that order dried over anhydrous magnesium sulfate After filtration the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography

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

Procedure: After dissolving 1-bromo-2-difluoromethylbenzene (3.23 g) in tetrahydrofuran (65 ml), the mixture was cooled to −78° C. After then adding n-butyllithium (2.64 M solution in hexane, 6.5 ml) and stirring for 30 minutes, N,N-dimethylformamide (2.4 ml) was added and stirring was continued for 3 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and then the mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and brine in that order and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (991 mg). extracted with ethyl acetate The organic layer was washed with water and brine in that order dried over anhydrous magnesium sulfate After filtration the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography

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

Procedure: A solution of n-BuLi (4.2 mL, 10.6 mmol) in THF was added to a solution of 1-bromo-2-(difluoromethyl)benzene 51 (2.0 g, 9.7 mmol) in THF (50 mL) at −78° C. The reaction mixture was stirred for 30 min and DMF (1.4 g, 19.3 mmol) was added. Stirring was continued for 1 h at −40° C. and the reaction was quenched by the addition of sat. aq NH4Cl. The crude mixture was extracted with Et2O, dried (MgSO4) and concentrated to give 52 (1.7 g, 94% yield). Stirring was continued for 1 h at −40° C. the reaction was quenched by the addition of sat. aq NH4Cl The crude mixture was extracted with Et2O dried (MgSO4) concentrated

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

Procedure: After dissolving 1-bromo-2-difluoromethylbenzene (3.23 g) in tetrahydrofuran (65 ml), the mixture was cooled to −78° C. After then adding n-butyllithium (2.64 M solution in hexane, 6.5 ml) and stirring for 30 minutes, N,N-dimethylformamide (2.4 ml) was added and stirring was continued for 3 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and then the mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and brine in that order and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (991 mg). extracted with ethyl acetate The organic layer was washed with water and brine in that order dried over anhydrous magnesium sulfate After filtration the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Prepared analogous to Example 1 starting from 2-(difluoromethyl)benzaldehyde and 4-Amino-N-phenethyl-2-(trifluoromethyl)nicotinamide. 1H NMR (400 MHz, CDCl3) δ 8.88 (d, 1H), 7.77 (d, 1H), 7.72 (d, 1H), 7.69 (t, 1H), 7.61 (t, 1H), 7.19 (m, 4H), 6.89 (m, 2H), 6.77 (t, 1H), 4.28 (m, 1H), 3.78 (m, 1H), 2.95 (m, 2H). MS m/z 446.4 (M+H)+.

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

Procedure: A mixture of (2-(difluoromethyl)phenyl)methanol (100 mg, 0.632 mmol) and manganese oxide (275 mg, 3.16 mmol) in dichloromethane was stirred at room temperature for twelve hours and then at 45° C. for 1 h. The reaction was filtered through celite and concentrated, to give 2-(difluoromethyl)benzaldehyde as an oil (99 mg). 1H NMR (400 MHz, CDCl3) δ 10.2 (s, 1H), 7.94 (d, 1H), 7.81 (d, 1H), 7.70 (m, 2H), 6.93 (t, 1H). The reaction was filtered through celite and concentrated

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

Procedure: A solution of n-BuLi (4.2 mL, 10.6 mmol) in THF was added to a solution of 1-bromo-2-(difluoromethyl)benzene 51 (2.0 g, 9.7 mmol) in THF (50 mL) at −78° C. The reaction mixture was stirred for 30 min and DMF (1.4 g, 19.3 mmol) was added. Stirring was continued for 1 h at −40° C. and the reaction was quenched by the addition of sat. aq NH4Cl. The crude mixture was extracted with Et2O, dried (MgSO4) and concentrated to give 52 (1.7 g, 94% yield). Stirring was continued for 1 h at −40° C. the reaction was quenched by the addition of sat. aq NH4Cl The crude mixture was extracted with Et2O dried (MgSO4) concentrated