2-(bromomethyl)-1,3,4-trifluorobenzene

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: 2,3,6-Trifluorobenzyl bromide (9.79 g, 43.3 mmol) and 4-chlorothiophenol (6.23 g, 43.3 mmol) were dissolved in 300 mL of THF. Triethylamine (4.59 g, 45.4 mmol) was added. The solution was stirred at room temperature overnight. 300 mL of EtOAc and 300 mL of water were added. The organic layers were washed with 200 mL 1N HCl solution, dried over Na2SO4 and concentrated. The residue was pure product (12.5 g, quant. yield). 1H NMR (CDCl3 400 MHz) δ 7.30 (d, J=8.8 Hz, 2H), 7.24 (d, J=8.8 Hz, 2H), 7.03 (m, 1H), 6.77 (m, 1H), 4.08 (s, 2H). The organic layers were washed with 200 mL 1N HCl solution dried over Na2SO4 concentrated

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

Procedure: 2,3,6-Trifluorobenzyl bromide (9.79 g, 43.3 mmol) and 4-chlorothiophenol (6.23 g, 43.3 mmol) were dissolved in 300 mL of THF. Triethylamine (4.59 g, 45.4 mmol) was added. The solution was stirred at room temperature overnight. 300 mL of EtOAc and 300 mL of water were added. The organic layers were washed with 200 mL 1N HCl solution, dried over Na2SO4 and concentrated. The residue was pure product (12.5 g, quant. yield). 1H NMR (CDCl3 400 MHz) δ 7.30 (d, J=8.8 Hz, 2H), 7.24 (d, J=8.8 Hz, 2H), 7.03 (m, 1H), 6.77 (m, 1H), 4.08 (s, 2H). The organic layers were washed with 200 mL 1N HCl solution dried over Na2SO4 concentrated

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

Procedure: 2,3,6-Trifluorobenzyl bromide (9.79 g, 43.3 mmol) and 4-chlorothiophenol (6.23 g, 43.3 mmol) were dissolved in 300 mL of THF. Triethylamine (4.59 g, 45.4 mmol) was added. The solution was stirred at room temperature overnight. 300 mL of EtOAc and 300 mL of water were added. The organic layers were washed with 200 mL 1N HCl solution, dried over Na2SO4 and concentrated. The residue was pure product (12.5 g, quant. yield). 1H NMR (CDCl3 400 MHz) δ 7.30 (d, J=8.8 Hz, 2H), 7.24 (d, J=8.8 Hz, 2H), 7.03 (m, 1H), 6.77 (m, 1H), 4.08 (s, 2H). The organic layers were washed with 200 mL 1N HCl solution dried over Na2SO4 concentrated

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

Procedure: 2,3,6-Trifluorobenzyl bromide (9.79 g, 43.3 mmol) and 4-chlorothiophenol (6.23 g, 43.3 mmol) were dissolved in 300 mL of THF. Triethylamine (4.59 g, 45.4 mmol) was added. The solution was stirred at room temperature overnight. 300 mL of EtOAc and 300 mL of water were added. The organic layers were washed with 200 mL 1N HCl solution, dried over Na2SO4 and concentrated. The residue was pure product (12.5 g, quant. yield). 1H NMR (CDCl3 400 MHz) δ 7.30 (d, J=8.8 Hz, 2H), 7.24 (d, J=8.8 Hz, 2H), 7.03 (m, 1H), 6.77 (m, 1H), 4.08 (s, 2H). The organic layers were washed with 200 mL 1N HCl solution dried over Na2SO4 concentrated

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

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

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3.00 g (12.81 mmol) of ethyl 8-hydroxy-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylate Example 17A, 3.27 g (14.1 mmol) of 2-(bromomethyl)-1,3,4-trifluorobenzene and 9.18 g (28.17 mmol) of caesium carbonate were initially charged in 183 ml of dry DMF and heated for 30 min in an oil bath warmed to 60° C. About 1.8 l of water were added to the reaction mi×ture, the mixture was stirred for 30 min and the solid was filtered off, washed with water and dried under reduced pressure. This gave 5.07 g of the title compound (99% of theory; purity about 96%). heated for 30 min in an oil bath the solid was filtered off washed with water dried under reduced pressure

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

Procedure: Ethyl 1-(4-fluorophenyl)-4-methyl-2-((2,3,6-trifluorobenzyl)thio)-1H-imidazole-5-carboxylate (58) was prepared in a similar manner as that described for the synthesis of compound 10 using 1-(4-fluorophenyl)-2-mercapto-4-methyl-1H-imidazole-5-carboxylate (57) (500 mg, 1.78 mmol), 2,3,6-trifluorobenzyl bromide (560 mg, 2.49 mmol) and potassium carbonate (736 mg, 6 mmol) in acetone (18 mL).

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

Procedure: Ethyl 1-(4-fluorophenyl)-4-methyl-2-((2,3,6-trifluorobenzyl)thio)-1H-imidazole-5-carboxylate (58) was prepared in a similar manner as that described for the synthesis of compound 10 using 1-(4-fluorophenyl)-2-mercapto-4-methyl-1H-imidazole-5-carboxylate (57) (500 mg, 1.78 mmol), 2,3,6-trifluorobenzyl bromide (560 mg, 2.49 mmol) and potassium carbonate (736 mg, 6 mmol) in acetone (18 mL).

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

Procedure: A solution of lithium bis(trimethylsilyl)amide (LiHMDS) (1M in THF, 26.6 mL, 26.6 mmol) was added to a solution of isobutyronitrile (2.4 mL, 26.6 mmol) in THF at −78° C. and stirred for 25 minutes. 2,3,6-trifluorobenzyl bromide (2.3 mL, 17.8 mmol) was added and the reaction was warmed to room temperature and stirred for 1.5 h. Water was added to quench the reaction and it was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to yield 2,2-dimethyl-3-(2,3,6-trifluorophenyl)propanenitrile (34) as a white solid. stirred for 1.5 h to quench the reaction and it was extracted with ethyl acetate The combined organic layers were dried over sodium sulfate filtered concentrated in vacuo