1,3-dibromo-5-tert-butylbenzene

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: step 1—A sealed tube containing 3,5-dibromo-tert-butylbenzene (1.00 g, 3.425 mmol, CASRN 129316-09-2), 37 (522 mg, 3.413 mmol), Pd(PPh3)4 (194 mg, 0.168 mmol) and Na2CO3 (942 mg, 8.888 mmol) and a mixture of MeOH/DCM (8/2 10 mL) was irradiated in a microwave synthesizer at 100° C. for 10 min. The organic volatiles were removed under reduced pressure. The residue was partitioned between EtOAc and water. The organic layer was washed with brine, dried (Na2SO4), filtered and concentrated. The crude residue was purified by SiO2 chromatography eluting with a EtOAc/hexane gradient (0 to 2% EtOAc) to afford 0.633 g (58%) of 3-(3-bromo-5-tert-butyl-phenyl)-2-methoxy-pyridine (122) as a colorless oil. step 1—A sealed tube was irradiated in a microwave synthesizer at 100° C. for 10 min The organic volatiles were removed under reduced pressure The residue was partitioned between EtOAc and water The organic layer was washed with brine dried (Na2SO4) filtered concentrated The crude residue was purified by SiO2 chromatography eluting with a EtOAc/hexane gradient (0 to 2% EtOAc)

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

実験手順: To a stirring solution of 34 mL of 1.6 M n-BuLi in hexanes in 20 mL of THF at −78° C. was added 8.15 g of 1,3-dibromo-5-tert-butylbenzene in 80 mL of THF dropwise over a period of 1 h. After 1 h at −78° C., 4.6 mL of B(OMe)3 was added, and after 20 min. the cold bath was removed and stirring continued with warming to r.t. After 1 h, EtOAc and 70 mL of 1 N HCl were added, and the layers were separated. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated. To a stirring mixture of the crude product in 105 mL of 1 N NaOH at 0° C. was added 22 mL of H2O2 (30 wt % in H2O) dropwise. After 25 min. 5 N HCl was added to a pH=1. Ethyl acetate was added, and the organic layer was washed with 80 mL of brine, dried over Na2SO4, filtered, and concentrated. Purification by flash silica gel chromatography (hexanes to 10% EtOAc/hexanes) provided 6.54 g of 3-bromo-5-tert-butylphenol as an orange oil with some impurity. after 20 min. the cold bath was removed After 1 h EtOAc and 70 mL of 1 N HCl were added the layers were separated The organic layer was washed with brine dried over Na2SO4 filtered concentrated To a stirring mixture of the crude product in 105 mL of 1 N NaOH at 0° C. was added 22 mL of H2O2 (30 wt % in H2O) dropwise After 25 min 5 N HCl was added to a pH=1 Ethyl acetate was added the organic layer was washed with 80 mL of brine dried over Na2SO4 filtered concentrated Purification by flash silica gel chromatography (hexanes to 10% EtOAc/hexanes)

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

実験手順: To a stirring solution of 2,6-dibromo-4-tert-butylaniline in 115 mL of EtOH was added 11.5 mL of concentrated H2SO4. To the stirring solution at 90° C. was added 8.8 g of NaNO2 in several portions. After 37 h, EtOAc and 120 mL of H2O were added, and the layers separated. The organic layer was washed with 40 mL of brine, dried over Na2SO4, filtered, and concentrated. Purification by flash silica gel chromatography (hexanes) provided 8.15 g of 1,3-dibromo-5-tert-butylbenzene as a yellow-brown oil with some impurity. the layers separated The organic layer was washed with 40 mL of brine dried over Na2SO4 filtered concentrated Purification by flash silica gel chromatography (hexanes)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1,3-dibromo-5-tert-butylbenzene (289 mg, 1 mmol) in DMF (20 mL) were added NaOMe (2 eq) and CuI (0.03 eq). The mixture was stirred at 80° C. for 3 h and then was poured into water and extracted with EA. The combined organic layers were washed with brine and dried over Na2SO4. After filtration, the filtrate was evaporated to give compound 14a as solid (200 mg, 82%). extracted with EA The combined organic layers were washed with brine dried over Na2SO4 After filtration the filtrate was evaporated

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1,3-dibromo-5-(tert-butyl)benzene (664 mg, 2.22 mmol) in toluene (15 mL) were added tri-n-butyl-1-ethoxyvinyl tin (965 mg, 2.66 mmol) and Pd(PPh3)2Cl2 (150 mg 0.22 mmol) under N2. The mixture was stirred at 95° C. for 3 h, evaporated, diluted with 1,4-dioxane and 2N HCl, stirred rapidly at 25° C. for 1 h and then extracted with EA. The combined organic layers were washed with brine, dried over Na2SO4, concentrated and purified by CC to afford compound P49a (310 mg, 55%). evaporated diluted with 1,4-dioxane and 2N HCl stirred rapidly at 25° C. for 1 h extracted with EA The combined organic layers were washed with brine dried over Na2SO4 concentrated purified by CC to afford compound P49a (310 mg, 55%)

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

実験手順: To a solution of 1,3-dibromo-5-(tert-butyl)benzene (316 mg, 1.05 mmol) in dry THF (15 mL), n-BuLi (1 mL, 2.5M) was added dropwise under N2 at −78° C. The mixture was stirred at this temperature for 1 h. Then oxetan-3-one (91 mg, 1.27 mmol) was added and the mixture was stirred at rt overnight, diluted with aq. NH4Cl (20 mL) and extracted with EA. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated to give the product P29a (120 mg, 40%) as a yellow solid. the mixture was stirred at rt overnight extracted with EA The combined organic layers were washed with brine dried over Na2SO4 concentrated to give the product P29a (120 mg, 40%) as a yellow solid

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

実験手順: To a solution of 1,3-dibromo-5-(tert-butyl)benzene (2.92 g, 10 mmol) in dioxane (20 mL) was added Pd(PPh3)4 (3.0 g, 2.6 mmol), prop-1-en-2-ylboronic acid (1.0 g, 12 mmol), K2CO3 (2.8 g, 20 mmol) and H2O (1 mL) under N2. The resulting mixture was stirred at 90° C. overnight, concentrated and purified by CC (hexane) to give compound P24a (2.5 g, 100%; 80% by GC/MS) as a liquid. concentrated purified by CC (hexane) to give compound P24a (2.5 g, 100%; 80% by GC/MS) as a liquid

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

実験手順: To a solution of 1,3-dibromo-5-tert-butylbenzene (404 mg) in dry THF (10 mL) was added n-BuLi (0.84 mL) at −78° C. and after 20 min, acetone was added dropwise to the above solution at −78° C. and the mixture was stirred at this temperature for 30 min and at rt for 1 h, diluted with sat. NH4Cl and extracted with EA (3×30 mL). The organic layer was dried over Na2SO4, evaporated and purified by CC to give compound P23a (380 mg, 70%) as a white solid. extracted with EA (3×30 mL) The organic layer was dried over Na2SO4 evaporated purified by CC to give compound P23a (380 mg, 70%) as a white solid

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,3-Dibromo-5-tert-butylbenzene (2.89 g, 10 mmol) in dioxane (160 mL) was stirred under Ar. Then DIPEA (3.09 mL, 16 mmol), Xantphos (0.28 g, 0.48 mmol) and Pd2(dba)3 (0.24 g, 0.24 mmol) were added and the reaction was heated to 100° C. Phenyl-methanethiol (0.94 mL, 8 mmol) was slowly added and the reaction was stirred for 6 h, quenched by the addition of H2O (15 mL) and extracted with EA (3×). The combined organic layers were washed with water, dried over Na2SO4, filtered, evaporated and purified by CC to afford compound P21a (1.7 g, 72%). quenched by the addition of H2O (15 mL) extracted with EA (3×) The combined organic layers were washed with water dried over Na2SO4 filtered evaporated purified by CC to afford compound P21a (1.7 g, 72%)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,3-Dibromo-5-tert-butylbenzene (50 g, 0.17 mol) was dissolved in anhydrous ether (200 mL) in a dried flask under nitrogen. The reaction mixture was cooled to −78° C. and stirred under nitrogen atmosphere. A 2.46 M solution of n-BuLi in hexanes (171.2 mL, 0.171 mol) was added dropwise to the above solution and the reaction mixture was stirred at −78° C. for 30 minute after complete addition of n-BuLi. After 30 minute of stirring at −78° C., the reaction mixture was warmed to −30° C. DMF (16 mL, 0.2 mol) was added to the above reaction mixture dropwise, keeping the reaction mixture below −20° C. After addition of DMF, the reaction mixture was warmed slowly to 0° C. (30 minute) and then stirring was continued overnight to obtain a yellow-orange solution. The reaction mixture was poured into 400 mL of chilled 10% aqueous HCl and the mixture was stirred for 15 minutes. The ether layer was separated, washed with water (2×250 mL), dried over anhydrous Na2SO4, filtered and evaporated in vacuo to give the product as a pale yellow viscous liquid. The crude product was dissolved in dichloromethane (250 mL) and passed through a small pad of silica gel (250 g). Evaporation of the solvent in vacuo gave the product as a pale yellow viscous liquid (41.2 g). the reaction mixture was stirred at −78° C. for 30 minute After 30 minute of stirring at −78° C. the reaction mixture was warmed to −30° C the reaction mixture below −20° C the reaction mixture was warmed slowly to 0° C. (30 minute) stirring to obtain a yellow-orange solution the mixture was stirred for 15 minutes The ether layer was separated washed with water (2×250 mL) dried over anhydrous Na2SO4 filtered evaporated in vacuo

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1,3-dibromo-5-tert-butylbenzene (2.92 g, 10.0 mmol, 1.0 eq), 1H-imidazole (0.69 g, 10.0 mmol, 1.0 eq), CuI (0.19 g, 1.0 mmol, 0.10 eq), K2CO3 (2.76 g, 20.0 mmol, 2.0 eq) and 2-(dimethylamino)acetic acid (0.21 g, 2.0 mmol, 0.20 eq) in DMSO (10 mL) was stirred at a temperature of 110° C. for four days under a nitrogen atmosphere, then cooled down to ambient temperature. The mixture was diluted with plenty of ethyl acetate and filtered. The filtrate was washed with water three times, dried over sodium sulfate, then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified through column chromatography on silica gel using hexane and ethyl acetate as an eluent to obtain the desired product, 1-(3-bromo-5-tert-butylphenyl)-1H-imidazole 7, as a brown sticky liquid (1.56 g in 56% yield). cooled down to ambient temperature filtered The filtrate was washed with water three times dried over sodium sulfate filtered the filtrate was concentrated under reduced pressure The residue was purified through column chromatography on silica gel