反应详情

To a round-bottomed flask were added 4-[(4-bromophenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenol (14) (0.105 g, 0.26 mmol), 4-dihydroxyborane-benzoic acid (0.093 g, 0.56 mmol, 2.2 eq), tetrakis(triphenylphosphine)palladium(0) (0.023 g, 0.02 mmol, 0.08 eq), aqueous Na2CO3 (2 M, 3 mL), and ethylene glycol dimethyl ether (5 mL). The reaction mixture was heated overnight at reflux with stirring under a nitrogen atmosphere. The reaction mixture was allowed to stand at RT under nitrogen for six days. To the reaction mixture were added 4-dihydroxyborane-benzoic acid (0.099 g, 0.60 mmol, 2.3 eq), tetrakis(triphenylphosphine)palladium(0) (0.031 g, 0.027 mmol, 0.10 eq), aqueous sodium carbonate (2 M, 2 mL), and ethylene glycol dimethyl ether (2 mL). The stirred reaction mixture was heated overnight at reflux under nitrogen. The reaction mixture was allowed to stand at RT under nitrogen for one week. The reaction mixture was partitioned between 1 N HCl (aqueous) and CH2Cl2. The organic phase was separated, washed with brine, dried over MgSO4, filtered, and the filtrate was concentrated to give the crude product as an oil. The crude product was partially purified by flash chromatography on silica gel with a CH2Cl2:MeOH (100:0 to 96:4) gradient to give 0.052 g of the impure product as a an oil. The impure product was purified by reverse phase preparative HPLC using a C18 column and an CH3CN:H2O (75:25 to 100:0) gradient with 0.05% TFA as a modifier to give 9.3 mg (8%) of compound 103 as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 0.89 (br s, 12H), 1.26 (br s, 2H), 1.93 (br s, 4H), 6.67 (d, J=8.5 Hz, 2H), 6.96 (d, J=8.4 Hz, 2H), 7.23 (d, J=8.1 Hz, 2H), 7.65 (d, J=8.1 Hz, 2H), 7.77 (d, J=8.2 Hz, 2H), 7.98 (d, J=8.4 Hz, 2H), 9.29 (s, 1H), 12.94 (br s, 1H).

1. temperatureThe reaction mixture was heated overnight
2. temperatureat reflux
3. customThe stirred reaction mixture
4. temperaturewas heated overnight
5. temperatureat reflux under nitrogen
6. waitto stand at RT under nitrogen for one week
7. customThe reaction mixture was partitioned between 1 N HCl (aqueous) and CH2Cl2
8. customThe organic phase was separated
9. washwashed with brine
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationthe filtrate was concentrated
13. customto give the crude product as an oil
14. customThe crude product was partially purified by flash chromatography on silica gel with a CH2Cl2:MeOH (100:0 to 96:4) gradient