反应详情

温度

60 °C

To a purged (Argon) sample of 4-Methylene-piperidine-1-carboxylic acid tert-butyl ester (727 mg, 3.68 mmol) was added 9-BBN (11.32 mL, 5.66 mmol). The mixture was stirred at 60° C. for two hours. After cooling to room temperature this solution was added to 5-Bromo-7-methyl-2-cyclopropylmethyl-2,3-dihydro-isoindol-1-one (794 mg, 2.83 mmol), Pd(dppf)Cl2 (115 mg, 0.142 mmol), DMF (25 mL), potassium carbonate (1.17 g, 8.49 mmol) and water (2.5 mL). The mixture was allowed to stir at 75° C. for 1.5 hours. The mixture was then cooled to room temperature and poured into water (3 mL). The product was extracted with ethyl acetate. The combined organic layers were washed with water three times, brine, dried over sodium sulphate, filtered and concentrated. Column chromatography (30% Ethyl acetate/hexanes) provided the title compound as a light yellow oil (777 mg, 53%). 1H NMR (300 MHz, CDCl3): δ 7.01 (s, 1H), 6.94 (s, 1H), 4.39 (s, 2H), 3.42 (d, 2H), 2.68 (s, 3H), 2.57 (s, 2H), 2.54 (d, 2H), 1.70-1.62 (m, 4H), 1.43 (s, 9H), 1.09 (d, 1H), 1.01 (m, 1H), 0.56-0.5 (m, 2H), 0.31-0.29 (m, 2H).

1. temperatureAfter cooling to room temperature this solution
2. stirringto stir at 75° C. for 1.5 hours
3. temperatureThe mixture was then cooled to room temperature
4. extractionThe product was extracted with ethyl acetate
5. washThe combined organic layers were washed with water three times, brine
6. dry with materialdried over sodium sulphate
7. filtrationfiltered
8. concentrationconcentrated