5-bromo-2-fluoro-1,3-dimethylbenzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (R)-2-Amino-hexanoic acid (0.840 g, 6.4 mmol), 5-bromo-2-fluoro-1,3-dimethyl-benzene (1.292 g, 6.4 mmol), CuI (0.122 g, 0.64 mmol), and K2CO3 (1.326 g, 9.6 mmol) were weighed into a Schlenk flask. To this was added 8 mL of dimethylacetamide and the resulting mixture vacuum-pumped and nitrogen-filled alternatively three times. After heating to 90° C. with stirring for 39 h, the reaction mixture was cooled to room temperature, diluted with 20 mL of ethyl acetate and 10 mL of water, and then acidified with concentrated HCl to pH=3. The layers were separated and the aqueous layer extracted with ethyl acetate (20 mL×5). The organic layers were combined and dried over anhydrous Na2SO4. Removal of the solvent under reduced pressure gave the title product which was used directly in the next step with further purification. LC-MS: tR=8.5 min, m/z 254 (M+H)+. the resulting mixture vacuum-pumped and nitrogen-filled alternatively three times the reaction mixture was cooled to room temperature The layers were separated the aqueous layer extracted with ethyl acetate (20 mL×5) dried over anhydrous Na2SO4 Removal of the solvent under reduced pressure

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (R)-2-Amino-hexanoic acid (0.840 g, 6.4 mmol), 5-bromo-2-fluoro-1,3-dimethyl-benzene (1.292 g, 6.4 mmol), CuI (0.122 g, 0.64 mmol), and K2CO3 (1.326 g, 9.6 mmol) were weighed into a Schlenk flask. To this was added 8 mL of dimethylacetamide and the resulting mixture vacuum-pumped and nitrogen-filled alternatively three times. After heating to 90° C. with stirring for 39 h, the reaction mixture was cooled to room temperature, diluted with 20 mL of ethyl acetate and 10 mL of water, and then acidified with concentrated HCl to pH=3. The layers were separated and the aqueous layer extracted with ethyl acetate (20 mL×5). The organic layers were combined and dried over anhydrous Na2SO4. Removal of the solvent under reduced pressure gave the title product which was used directly in the next step with further purification. LC-MS: tR=8.5 min, m/z 254 (M+H)+. the resulting mixture vacuum-pumped and nitrogen-filled alternatively three times the reaction mixture was cooled to room temperature The layers were separated the aqueous layer extracted with ethyl acetate (20 mL×5) dried over anhydrous Na2SO4 Removal of the solvent under reduced pressure

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

実験手順: To a mixture of 4-Bromo-2,6-dimethylaniline (8.3 g, 42 mmol) at 5° C. and H2O (50 mL) was added conc H2SO4 (6.25 mL). NaNO2 (4.1 g) was added in portions until an excess was indicated by starch iodide paper. Water (30 mL) was added to make the mixture homogeneous. After transferring to a plastic container, HBF4 (50%, 13.7 g) was added dropwise with stirring. The resultant white precipitate was collected by vacuum filtration, washed with H2O (30 mL), MeOH (30 mL), and Et2O (60 mL), and dried over P2O5 under vacuum for 16 h. The solid was then heated in a glass flask with an open flame until all the solid had decomposed. The remaining liquid was diluted with Et2O (50 mL) and 0.5 M NaOH (30 mL). The organic layer was separated, washed with 0.5 M NaOH (25 mL), H2O (25 mL), brine (25 mL), dried (MgSO4), and concentrated in vacuo yielding 6.06 g (72%) of 1-bromo-4-fluoro-3,5-dimethylbenzene as a pale yellow liquid. was added dropwise The resultant white precipitate was collected by vacuum filtration washed with H2O (30 mL), MeOH (30 mL), and Et2O (60 mL) dried over P2O5 under vacuum for 16 h The solid was then heated in a glass flask with an open flame until all the solid The remaining liquid was diluted with Et2O (50 mL) and 0.5 M NaOH (30 mL) The organic layer was separated washed with 0.5 M NaOH (25 mL), H2O (25 mL), brine (25 mL) dried (MgSO4) concentrated in vacuo

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add 5-bromo-2-fluoro-1,3-dimethyl-benzene (3.5 g, 17.2 mmol) to dimethylformamide (DMF, 30 mL) at ambient temperature followed by sodium thiomethoxide (1.32 g, 17.9 mmol). Heat at 50° C. for 8 hours and dilute with water (10 mL) and diethyl ether (100 mL). Separate the layers, wash the organics with brine, and dry with magnesium sulfate before concentrating to a residue. Chromatograph the residue on a SiO2 column eluting with diethyl ether (20%) in hexane to give 566 mg (14%) of 5-bromo-1,3-dimethyl-2-methylsulfanyl-benzene. Separate the layers wash the organics with brine dry with magnesium sulfate before concentrating to a residue Chromatograph the residue on a SiO2 column eluting with diethyl ether (20%) in hexane

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add 5-bromo-2-fluoro-1,3-dimethyl-benzene (3.5 g, 17.2 mmol) to dimethylformamide (DMF, 30 mL) at ambient temperature followed by sodium thiomethoxide (1.32 g, 17.9 mmol). Heat at 50° C. for 8 hours and dilute with water (10 mL) and diethyl ether (100 mL). Separate the layers, wash the organics with brine, and dry with magnesium sulfate before concentrating to a residue. Chromatograph the residue on a SiO2 column eluting with diethyl ether (20%) in hexane to give 566 mg (14%) of 5-bromo-1,3-dimethyl-2-methylsulfanyl-benzene. Separate the layers wash the organics with brine dry with magnesium sulfate before concentrating to a residue Chromatograph the residue on a SiO2 column eluting with diethyl ether (20%) in hexane

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add 5-bromo-2-fluoro-1,3-dimethyl-benzene (3.5 g, 17.2 mmol) to dimethylformamide (DMF, 30 mL) at ambient temperature followed by sodium thiomethoxide (1.32 g, 17.9 mmol). Heat at 50° C. for 8 hours and dilute with water (10 mL) and diethyl ether (100 mL). Separate the layers, wash the organics with brine, and dry with magnesium sulfate before concentrating to a residue. Chromatograph the residue on a SiO2 column eluting with diethyl ether (20%) in hexane to give 566 mg (14%) of 5-bromo-1,3-dimethyl-2-methylsulfanyl-benzene. Separate the layers wash the organics with brine dry with magnesium sulfate before concentrating to a residue Chromatograph the residue on a SiO2 column eluting with diethyl ether (20%) in hexane

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: To a stirred solution of 5-bromo-2-fluoro-1,3-dimethylbenzene (5.0 g, 25 mmol) in carbon tetrachloride (100.0 mL) was added N-bromosuccinimide (4.11 g, 23.1 mmol) and benzoyl peroxide (100.0 mg, 0.017 mmol). The reaction was heated at reflux for 7 hours. The reaction was filtered and the filtrate washed with 2N HCl, saturated aqueous sodium bicarbonate, water and brine. The organic phase was dried over sodium sulfate, filtered and concentrated. The residue was flash chromatographed (5% EtoAc/Haptanes) to obtain 6.56 g of 5-bromo-1-(bromomethyl)-2-fluoro-3-methylbenzene as an oil product. 1H NMR (400 MHz, CDCl3) δ ppm 2.22-2.36 (s, 3 H) 4.42 (d, J=0.98 Hz, 2 H) 7.21-7.37 (m, 2 H) The reaction was heated at reflux for 7 hours The reaction was filtered the filtrate washed with 2N HCl, saturated aqueous sodium bicarbonate, water and brine The organic phase was dried over sodium sulfate filtered concentrated chromatographed (5% EtoAc/Haptanes)

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

実験手順: To a mixture of 4-Bromo-2,6-dimethylaniline (8.3 g, 42 mmol) at 5° C. and H2O (50 mL) was added conc H2SO4 (6.25 mL). NaNO2 (4.1 g) was added in portions until an excess was indicated by starch iodide paper. Water (30 mL) was added to make the mixture homogeneous. After transferring to a plastic container, HBF4 (50%, 13.7 g) was added dropwise with stirring. The resultant white precipitate was collected by vacuum filtration, washed with H2O (30 mL), MeOH (30 mL), and Et2O (60 mL), and dried over P2O5 under vacuum for 16 h. The solid was then heated in a glass flask with an open flame until all the solid had decomposed. The remaining liquid was diluted with Et2O (50 mL) and 0.5 M NaOH (30 mL). The organic layer was separated, washed with 0.5 M NaOH (25 mL), H2O (25 mL), brine (25 mL), dried (MgSO4), and concentrated in vacuo yielding 6.06 g (72%) of 1-bromo-4-fluoro-3,5-dimethylbenzene as a pale yellow liquid. was added dropwise The resultant white precipitate was collected by vacuum filtration washed with H2O (30 mL), MeOH (30 mL), and Et2O (60 mL) dried over P2O5 under vacuum for 16 h The solid was then heated in a glass flask with an open flame until all the solid The remaining liquid was diluted with Et2O (50 mL) and 0.5 M NaOH (30 mL) The organic layer was separated washed with 0.5 M NaOH (25 mL), H2O (25 mL), brine (25 mL) dried (MgSO4) concentrated in vacuo

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (R)-2-Amino-hexanoic acid (0.840 g, 6.4 mmol), 5-bromo-2-fluoro-1,3-dimethyl-benzene (1.292 g, 6.4 mmol), CuI (0.122 g, 0.64 mmol), and K2CO3 (1.326 g, 9.6 mmol) were weighed into a Schlenk flask. To this was added 8 mL of dimethylacetamide and the resulting mixture vacuum-pumped and nitrogen-filled alternatively three times. After heating to 90° C. with stirring for 39 h, the reaction mixture was cooled to room temperature, diluted with 20 mL of ethyl acetate and 10 mL of water, and then acidified with concentrated HCl to pH=3. The layers were separated and the aqueous layer extracted with ethyl acetate (20 mL×5). The organic layers were combined and dried over anhydrous Na2SO4. Removal of the solvent under reduced pressure gave the title product which was used directly in the next step with further purification. LC-MS: tR=8.5 min, m/z 254 (M+H)+. the resulting mixture vacuum-pumped and nitrogen-filled alternatively three times the reaction mixture was cooled to room temperature The layers were separated the aqueous layer extracted with ethyl acetate (20 mL×5) dried over anhydrous Na2SO4 Removal of the solvent under reduced pressure

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

実験手順: To a mixture of 4-Bromo-2,6-dimethylaniline (8.3 g, 42 mmol) at 5° C. and H2O (50 mL) was added conc H2SO4 (6.25 mL). NaNO2 (4.1 g) was added in portions until an excess was indicated by starch iodide paper. Water (30 mL) was added to make the mixture homogeneous. After transferring to a plastic container, HBF4 (50%, 13.7 g) was added dropwise with stirring. The resultant white precipitate was collected by vacuum filtration, washed with H2O (30 mL), MeOH (30 mL), and Et2O (60 mL), and dried over P2O5 under vacuum for 16 h. The solid was then heated in a glass flask with an open flame until all the solid had decomposed. The remaining liquid was diluted with Et2O (50 mL) and 0.5 M NaOH (30 mL). The organic layer was separated, washed with 0.5 M NaOH (25 mL), H2O (25 mL), brine (25 mL), dried (MgSO4), and concentrated in vacuo yielding 6.06 g (72%) of 1-bromo-4-fluoro-3,5-dimethylbenzene as a pale yellow liquid. was added dropwise The resultant white precipitate was collected by vacuum filtration washed with H2O (30 mL), MeOH (30 mL), and Et2O (60 mL) dried over P2O5 under vacuum for 16 h The solid was then heated in a glass flask with an open flame until all the solid The remaining liquid was diluted with Et2O (50 mL) and 0.5 M NaOH (30 mL) The organic layer was separated washed with 0.5 M NaOH (25 mL), H2O (25 mL), brine (25 mL) dried (MgSO4) concentrated in vacuo