4-bromo-1-(bromomethyl)-2-(trifluoromethyl)benzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Treat a mixture of 4-bromo-2-(trifluoromethyl)benzaldehyde (6.52 g, 25.8 mmol) and methanol (250 mL) in a 500 mL flask with sodium borohydride (778 mg, 20.6 mmol). Stir the reaction at room temperature for 1 hour then dilute with ethyl acetate (300 mL). Wash with water (2×200 mL) and saturated sodium chloride solution (1×200 mL), then dry over anhydrous magnesium sulfate. After filtering, concentrate the solution under vacuum to dryness. Add dimethylformamide (250 mL) to the residue and cool in an ice bath before treating with carbon tetrabromide (12.78 g, 38.5 mmol) and triphenylphosphine (10.11 g, 38.5 mmol) for 3 hours. Add ethyl acetate (300 mL) and wash with water (2×200 mL) then saturated sodium chloride solution (1×200 mL). Dry over anhydrous magnesium sulfate and concentrate under vacuum. Purify the crude product via silica gel chromatography eluting with hexanes to afford 6.02 g (74%) of the product as a clear oil: 1H NMR (300 MHz, CDCl3) δ 7.78 (d, 1H, J=1.9 Hz), 7.68 (dd, 1H, J=1.9 Hz, J=8.3 Hz), 7.47 (d, 1H, J=8.3 Hz), 4.57 (s, 2H). Treat the reaction at room temperature for 1 hour Wash with water (2×200 mL) and saturated sodium chloride solution (1×200 mL) dry over anhydrous magnesium sulfate After filtering concentrate the solution under vacuum to dryness Add dimethylformamide (250 mL) to the residue and cool in an ice bath Add ethyl acetate (300 mL) and wash with water (2×200 mL) Dry over anhydrous magnesium sulfate concentrate under vacuum Purify the crude product via silica gel chromatography eluting with hexanes

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Potassium cyanide (630 mg) was added to an emulsion of 4-bromo-1-bromomethyl-2-trifluoromethylbenzene (3.86 g) in ethanol (15 mL)-water (5 mL), and the mixture was stirred at 70° C. for three hours and 15 minutes. Water and ethyl acetate were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Wakogel C-200; elution solvent:heptane:ethyl acetate=9:1) to obtain 2.28 g of the title compound. The property values of the compound are as follows. the organic layer was separated The resulting organic layer was washed with brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography (carrier: Wakogel C-200; elution solvent:heptane:ethyl acetate=9:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Bromosuccinimide (2.6 g) and 2,2′-azobis(isobutyronitrile) (35 mg) were added to a solution of 5-bromo-2-methylbenzotrifluoride (CAS #86845-27-4, 3.5 g) in carbon tetrachloride (35 mL), and the mixture was heated under reflux for five hours. The reaction solution was ice-cooled and then the insoluble matter was removed by filtration. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Wakogel C-200; elution solvent: heptane) to obtain 3.86 g of the title compound. The property values of the compound are as follows. the mixture was heated under reflux for five hours cooled the insoluble matter was removed by filtration The filtrate was concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography (carrier: Wakogel C-200; elution solvent: heptane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromo-2-trifluoromethylbenzyl bromide (2.4 g) in acetone (20 ml) was added potassium thioacetate (1.04 g). The reaction mixture was heated to reflux for 4 hours. The reaction mixture was allowed to cool to ambient temperature and was then filtered through a plug of silica gel. Further acetone (30 ml) was passed through the silica gel (30 ml). The combined filtrate was concentrated to give thioacetic acid S-(4-bromo-2-trifluoromethyl-benzyl) ester as a dark liquid (2.275 g). 1H-NMR (400 MHz, CDCl3): 7.75 (s, 1H), 7.60 (d, 1H), 7.42 (d, 1H), 4.25 (s, 2H), 2.36 (s, 3H) ppm. The reaction mixture was heated to reflux for 4 hours was then filtered through a plug of silica gel The combined filtrate was concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-methyl-3-trifluorobromobenzene (33.26 g, 104.261 mmol) from step 1 above, KCN (20.43 g, 313.67 mmol) and tetrabutylammonium bromide (3.37 g, 10.45 mmol) in CH2Cl2/H2O 1:1 (300 mL) was stirred at room temperature for 4 hours. The layers were separated and the organic layer washed with H2O (100 mL) 1N HCl (100 mL), brine, dried over Na2SO4 and then concentrated to a brown oil which was purified by flash column chromatography (0% to 20% EtOAc in hexanes) to give the product as a clear oil (14.9 g, 54%). 1H NMR (400 MHz, CDCl3) δ 3.91 (s, 2H), 7.57 (d, J=8.3 Hz, 1 H), 7.75 (dd, J=8.3, 2 Hz, 1 H), 7.84 (d, J=2 Hz, 1 H). The layers were separated the organic layer washed with H2O (100 mL) 1N HCl (100 mL), brine dried over Na2SO4 concentrated to a brown oil which was purified by flash column chromatography (0% to 20% EtOAc in hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-methyl-3-trifluorobromobenzene (33.26 g, 104.261 mmol) from step 1 above, KCN (20.43 g, 313.67 mmol) and tetrabutylammonium bromide (3.37 g, 10.45 mmol) in CH2Cl2/H2O 1:1 (300 mL) was stirred at room temperature for 4 hours. The layers were separated and the organic layer washed with H2O (100 mL) 1N HCl (100 mL), brine, dried over Na2SO4 and then concentrated to a brown oil which was purified by flash column chromatography (0% to 20% EtOAc in hexanes) to give the product as a clear oil (14.9 g, 54%). 1H NMR (400 MHz, CDCl3) δ 3.91 (s, 2H), 7.57 (d, J=8.3 Hz, 1 H), 7.75 (dd, J=8.3, 2 Hz, 1 H), 7.84 (d, J=2 Hz, 1 H). The layers were separated the organic layer washed with H2O (100 mL) 1N HCl (100 mL), brine dried over Na2SO4 concentrated to a brown oil which was purified by flash column chromatography (0% to 20% EtOAc in hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-(tert-Butoxycarbonyl)-4-piperidinemethanol (400 mg) was added to a mixture of 60% sodium hydride (90 mg) and DMF (11 mL) under ice-cooling in a nitrogen atmosphere, and the mixture was stirred for 10 minutes. A solution of 4-bromo-1-(bromomethyl)-2-(trifluoromethyl)benzene (550 mg) in DMF (2 mL) was added to the mixture under ice-cooling. After the reaction mixture was stirred for 30 minutes under ice-cooling, the temperature of the reaction mixture was raised to room temperature, and stirring was performed for 30 minutes. After a saturated aqueous ammonium chloride solution was added to the reaction mixture, extraction thereof was performed using an EtOAc-Hex mixed solvent (1:1), and the extract was washed with water and saturated brine. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hex:EtOAc=99:1 to 90:10), whereby tert-butyl 4-({[4-bromo-2-(trifluoromethyl)benzyl]oxy}methyl)piperidine-1-carboxylate (598 mg) was obtained as a pale yellow oil. cooling in a nitrogen atmosphere cooling After the reaction mixture was stirred for 30 minutes under ice- cooling stirring was performed for 30 minutes mixed solvent (1:1) the extract was washed with water and saturated brine The organic layer was dried over MgSO4 filtered the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (Hex:EtOAc=99:1 to 90:10)