4-fluoro-2-methyl-1-(trifluoromethyl)benzene

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

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

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

Procedure: To a −78° C. flask containing THF (7 mL) was added s-BuLi (10 mL of a 1.4 M solution in cyclohexane, 14.0 mmol). To this −78° C. solution was added a solution of 4-fluoro-2-methyl-1-(trifluoromethyl)benzene (2.0 g, 11.23 mmol) in heptanes (7 mL) over 20 minutes. The reaction was stirred at −78° C., for 1 hour and then DMF (1.5 mL) was added. Next, 1N HCl (30 mL) was added, and the reaction was warmed to room temperature and stirred for 10 minutes. The mixture was extracted with hexanes (75 mL) and the organic layer was washed with water and brine (20 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel afforded 2-fluoro-4-methyl-5-(trifluoromethyl)benzaldehyde. Rf=0.44 (15% EtOAc/hexanes). 1H NMR (CDCl3, 500 MHz) δ 10.31 (s, 1H), 8.14 (d, J=6.6 Hz, 1H), 7.13 (d, J=10.5 Hz, 1H), 2.56 (d, J=1.3 Hz, 3H). the reaction was warmed to room temperature stirred for 10 minutes The mixture was extracted with hexanes (75 mL) the organic layer was washed with water and brine (20 mL each) The organic layer was dried over Na2SO4 filtered concentrated Purification of the residue by flash chromatography on silica gel

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

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

Procedure: 4-Fluoro-2-methyl-1-(trifluoromethyl)benzene (5.6 mmol, 1 g) was dissolved in concentrated sulphuric acid (7 ml) and cooled to 0° C.; KNO3 (1 eq., 5.6 mmol, 566 mg) was added at to 0° C. in one pot and the mixture was stirred at to 0° C. for 4 hours. The crude mixture was poured onto ice and extracted with ethyl acetate; the organics were combined dried over Na2SO4, filtered and the solvent was evaporated to afford the title compound, 1.1 g, 88%. extracted with ethyl acetate the organics were combined dried over Na2SO4 filtered the solvent was evaporated

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

Procedure: To a −78° C. flask containing THF (7 mL) was added s-BuLi (10 mL of a 1.4 M solution in cyclohexane, 14.0 mmol). To this −78° C. solution was added a solution of 4-fluoro-2-methyl-1-(trifluoromethyl)benzene (2.0 g, 11.23 mmol) in heptanes (7 mL) over 20 minutes. The reaction was stirred at −78° C., for 1 hour and then DMF (1.5 mL) was added. Next, 1N HCl (30 mL) was added, and the reaction was warmed to room temperature and stirred for 10 minutes. The mixture was extracted with hexanes (75 mL) and the organic layer was washed with water and brine (20 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel afforded 2-fluoro-4-methyl-5-(trifluoromethyl)benzaldehyde. Rf=0.44 (15% EtOAc/hexanes). 1H NMR (CDCl3, 500 MHz) δ 10.31 (s, 1H), 8.14 (d, J=6.6 Hz, 1H), 7.13 (d, J=10.5 Hz, 1H), 2.56 (d, J=1.3 Hz, 3H). the reaction was warmed to room temperature stirred for 10 minutes The mixture was extracted with hexanes (75 mL) the organic layer was washed with water and brine (20 mL each) The organic layer was dried over Na2SO4 filtered concentrated Purification of the residue by flash chromatography on silica gel