| 32.8% |
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 80℃;Inert atmosphere; |
2 -Bromo- 1,3 -dimethyl benzene (20. Og, 108.04 mmol) and 3-formylphenylboronic acid (19.43g, 129.64 mmol) were dissolved in mixture of 1M aqueous solution of sodium carbonate (292 mL), ethanol (100 mL) and toluene (300 mL). The reaction mixture was degassed with argon gas for 10 min and Pd(PPh3)4 (6.24 g, 5.402mmol) was added. Then the reaction was heated to 80C for 18 h under inert atmosphere. The solution was cooled to RT and filtered through celite. The filtrate was concentrated and the aq. layer extracted with ethyl acetate. The organic layer was dried over Na2S04, and concentrated. The crude compound was purified by column chromatography on silica gel (230-400 mesh) using 2-4% of ethyl acetate in pet-ether as an eluent to afford Compound l-2a (7.5g, 32.8%). LC-MS: 2.36mins, [M+H]+ 211 |
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With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 80℃; for 12h;Inert atmosphere; |
General procedure: Step 1: The substituted bromobenzene (1 equiv) and (3-formylphenyl)boronic acid or (4-formylphenyl) boronic acid (1 equiv) were dissolved in a mixture of 1M sodium carbonate aqueous solution (15mL), EtOH (5mL) and toluene (15mL). After nitrogen substitution, Pd(PPh3)4 (0.05 equiv) was added. The reaction mixture was stirred at 80C under nitrogen atmosphere for 12h. The reaction mixture was cooled, and water (15mL) was added. The mixture was diluted with AcOEt (15mL), and the insoluble material was filtered off through Celite. The organic layer of the filtrate was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography using a mixture of petroleum ether/ethyl acetate (10:1, v/v) as eluent to afford the desired product 2a-r, 5a and 5b as a solid. Step 2: To a solution of 2a-r, 5a or 5b (1 equiv) in MeOH (10mL) and THF (20mL) was added portionwise sodium borohydride (3 equiv) at 0C and the mixture was stirred at 0C for 1h. The reaction mixture was pouring into ice water (10mL), and extracted with ethyl acetate (3×15mL), the organic fractions were combined, washed with saturated brine (2×15mL) prior to drying over anhydrous sodium sulfate. After filtration and concentrate using a rotary evaporator, the residue was used in next step without further purification. To a solution of the obtained solid (1 equiv) in dichloromethane (20mL) was slowly added thionyl chloride (6 equiv) and a catalytic amount of DMF at room temperature. After stirring at 40C for 4h, the reaction was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using a mixture of petroleum ether/ethyl acetate (20:1, v/v) as eluent to afford the desired product. 4.1.2 3'-(chloromethyl)-2,6-dimethyl-1,1'-biphenyl (3a) (0020) Yield: 65%; 1H NMR (300MHz, CDCl3) δ: 7.44-7.39 (m, 1H), 7.34 (d, J=7.9Hz, 1H), 7.07-7.19 (m, 5H), 4.52 (s, 2H), 1.97 (s, 6H). |
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