| 80% |
With sulfuric acid In dichloromethane at 15 - 20℃; for 2h; Inert atmosphere; |
2 Example 2 Preparation of Compound 2
Under the protection of nitrogen, 133.75 mmol of 1-adamantanol, 127.38 mmol of 2-bromophenol, and 220 mL of dichloromethane were added to the reaction flask. After the addition was completed, the solution was stirred and dissolved at room temperature, and then the temperature was lowered to 15 ° C., and concentrated sulfuric acid was added dropwise while holding. After the dropwise addition, the reaction was incubated for 2 h and then quenched by adding water. Separated, extracted, washed with water, dried, filtered, and concentrated. Pass the mixed solvent of dichloromethane and n-heptane through the column and recrystallize to LC> 95%. Drying gave 4-((3r, 5r, 7r) -adamantane-1-yl) -2-bromophenol as a white solid. Yield: 80%. |
| 80% |
With sulfuric acid In dichloromethane at 10 - 20℃; for 2h; Inert atmosphere; |
Preparation of intermediate IV
Under the protection of nitrogen, add 1-adamantanol (20.33g, 133.75mmol) to the reaction flask,2-bromophenol (22g, 127.38mmol, dichloromethane 220mL,After addition, stir at room temperature to dissolve,After that, the temperature was lowered to 10-20 ° C, and concentrated sulfuric acid (14.5mL, 267.5mmol) was added dropwise.After the dropwise addition, the reaction was incubated for 2 hours, and then quenched with water.The reaction system was separated, the aqueous phase was extracted with dichloromethane, and the organic phases were combined and washed with water.The organic phase is dried, filtered to remove the desiccant, and the organic phase is concentrated.The concentrate was passed through a column with a mixed solvent of methylene chloride and n-heptane,The product purified through the column was recrystallized to HPLC purity> 95%.Dry to get intermediate 1-3.Yield: 80%. |
| 42% |
With sulfuric acid; acetic acid In dichloromethane at 20℃; for 72h; |
1 4-(adamantan-l-yl)-2-bromophenol (S5).
To a mixture of 2-bromophenol (1.475g, 8.526 mmol) and 1-adamantol (1.298g, 8.526 mmol) in CH2CI2 (4 mL) was added 5: 1 AcOH:H2S04 (3 mL), and the reaction was stirred at room temperature for 3 days. The reaction poured into water and quenched with sat. NaHCCb, then extracted with CH2CI2 3x. The combined organic layers were washed with water and brine, dried over Na2S04, filtered, concentrated, and purified by column (0581) chromatography (loaded crude oil in hexanes, 0→ 2% EtOAc/hexanes), yielding the title compound as a white solid (l . lOOg, 42% yield). NMR (500 MHz, CDCb) δ 7.41 (d, J = 2.3 Hz, 1H), 7.21 (dd, J = 8.5, 2.3 Hz, 1H), 6.98 - 6.95 (m, 1H), 5.34 (s, 1H), 2.08 (s, 3H), 1.85 (d, J = 2.6 Hz, 6H), 1.81 - 1.70 (m, 6H); 13C NMR (125 MHz, CDCb) δ 150.10, 145.54, 128.70, 125.83, 115.68, 110.16, 68.11, 43.40, 36.78, 35.83, 29.02, 25.74; HRMS Accurate mass (ES+): Found 307.0711, Ci6H2o79BrO (M+H+) requires 307.0698. |
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