(5-bromo-2-fluorophenyl)methanol

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:

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

Procedure: In analogy to the procedure described for the synthesis example 71 (step 1), the title compound {2-fluoro-5-[2-(5-trifluoromethyl-pyridin-2-yl)-ethylamino]-phenyl}-methanol (MS m/e: 315.1 [M+H]+) was prepared from (5-bromo-2-fluoro-phenyl)-methanol instead of 6-bromo-2,3-dihydro-benzofuran and 2-(5-trifluoromethyl-pyridin-2-yl)-ethylamine instead of 2-(6-trifluoromethyl-pyridin-3-yl)-ethylamine. In analogy to the procedure described for the synthesis example 71 (step 1)

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

Procedure: In a 25 ml round bottom flask, 2-[1-(t-butoxycarbonyl)piperidin-3-yl]ethyl bromide (1.011 g, 3.46 mmol) was dissolved in N,N-dimethylformamide (9 ml). Sodium iodide (1.037 g, 6.92 mmol) was added and the resulting mixture was stirred at ambient temperature for ten minutes. The 2-fluoro-5-bromobenzyl alcohol (0.852 g, 4.15 mmol) and sodium hydride (60%, 208 mg, 5.19 mmol) were then added and the resulting mixture began to froth and exotherm. After thirty minutes, the solution cooled and solidified. Three milliliters of N,N-dimethylformamide was added and the mass was slurried and stirred for three more hours. The progress of the reaction was monitored by thin layer chromatography. The reaction mixture was partitioned between brine and diethyl ether. The organic fraction was washed six times with brine, and then dried over sodium sulfate. The desired title product was further purified by liquid chromatography. After thirty minutes the solution cooled stirred for three more hours The reaction mixture was partitioned between brine and diethyl ether The organic fraction was washed six times with brine dried over sodium sulfate The desired title product was further purified by liquid chromatography

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

Procedure: In a 50 ml flask, under a nitrogen atmosphere, 2-fluoro-5-bromobenzyl alcohol (2.139 g, 10.4 mmol) was dissolved in N,N-dimethylformamide (25 ml). To this solution sodium hydride (60%, 625 mg, 15.6 mmol) was added and the resulting mixture was stirred for twenty minutes. To the reaction mixture 5-chloropentyl bromide was added and the resulting mixture was stirred for two hours at ambient temperature. The progress of the reaction was monitored by thin layer chromatography. Sodium iodide (3.127 g, 20.9 mmol) was added and the resulting mixture was stirred at ambient temperature for three hours. The reaction mixture was diluted with diethyl ether and washed seven times with brine. The solvents were removed in vacuo. The title intermediate was further purified by silica gel. the resulting mixture was stirred for two hours at ambient temperature the resulting mixture was stirred at ambient temperature for three hours washed seven times with brine The solvents were removed in vacuo The title intermediate was further purified by silica gel

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

Procedure: In a 250 ml round bottom flask, under a nitrogen atmosphere, 2-fluoro-5-bromobenzyl alcohol (5.85 g, 28.5 mmol) was dissolved in diethy ether (125 ml). To this solution triphenylphosphine (9.73 g, 37.1 mmol) and carbon tetrabromide (12.30 g, 37.1 mmol) were added. The resulting mixture was stirred at ambient temperature for about three hours. The progress of the reaction was monitored by thin layer chromatography. The mixture was then stirred at ambient temperature for about 19 additional hours. The reaction mixture was filtered and washed with cold diethyl ether. The filtrate was evaporated, yielding a light yellow oil. The oil was further purified by chromatography on a silica gel with hexanes. The desired fractions were purified by evaporation to yield 5.8 grams of the desired title intermediate. The material slowly crystallized upon standing. The mixture was then stirred at ambient temperature for about 19 additional hours The reaction mixture was filtered washed with cold diethyl ether The filtrate was evaporated yielding a light yellow oil The oil was further purified by chromatography on a silica gel with hexanes The desired fractions were purified by evaporation

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

Procedure: An amount of 3-[1-(t-butoxycarbonyl)piperidin-3-yl]propyl bromide (180 mg, 0.588 mmol) was dissolved in N,N-dimethylformamide (1.5 ml) in a 10 ml flask under a nitrogen atmosphere. Sodium iodide (176 mg, 1.18 mmol) was added at ambient temperature, and the resulting mixture was stirred for ten minutes. The reaction mixture was treated with 2-fluoro-5-bromobenzyl alcohol (121 mg, 0.588 mmol), delivered as a solution in 0.5 ml of N,N-dimethylformamide. To this mixture was then added sodium hydride (60%, 35 mg, 0.882 mmol) and the resulting mixture was stirred at ambient temperature for three hours. The progress of the reaction was monitored by thin layer chromatography. The reaction mixture was partitioned between 1 M potassium carbonate and methylene chloride. The aqueous fraction was back extracted with methylene chloride. The organic fractions were combined, and dried over sodium sulfate. The solvents were removed in vacuo. The desired title product was further purified by liquid chromatography. The reaction mixture was partitioned between 1 M potassium carbonate and methylene chloride The aqueous fraction was back extracted with methylene chloride dried over sodium sulfate The solvents were removed in vacuo The desired title product was further purified by liquid chromatography

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

Procedure: To a solution of (5-bromo-2-fluorophenyl)methanol (5.00 g) in THF (100 ml) was added 60% sodium hydride (1.08 g) at 0° C., and the mixture was stirred at room temperature for 30 min. Methyl iodide (3.80 ml) was added, and the mixture was stirred for 1.5 h. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate, washed with saturated brine and dried. The solvent was evaporated under reduced pressure and the residue was purified by column chomatography (eluent, hexane→hexane:ethyl acetate=50:1) to give the title compound (4.86 g) as a brown oil. the mixture was stirred for 1.5 h the mixture was extracted with ethyl acetate washed with saturated brine dried The solvent was evaporated under reduced pressure the residue was purified by column chomatography (eluent, hexane→hexane:ethyl acetate=50:1)