反应详情

温度

-78 °C

To a solution of diisopropylamine (1.11 mL, 7.87 mmol) in 2-methyltetrahydrofuran (37 mL) at −5° C. was added n-BuLi (3.0 mL, 2.5 M in hexanes, 7.49 mmol) slowly. After 20 minutes, the reaction was cooled to −78° C. and Aripiprazole (1.68 g, 3.74 mmol) was added. After a further 10 minutes, hexylchloroformate (1.53 mL, 9.37 mmol) was added. The reaction was held at −78° C. for 2 hours before allowing to warm to room temperature overnight. The reaction was quenched with saturated aqueous ammonium chloride solution (30 mL) and extracted with ethyl acetate (2×30 mL). The organics were combined, washed with saturated aqueous sodium hydrogen carbonate solution (30 mL), brine (30 mL), dried over MgSO4 and concentrated. The crude product was purified by column chromatography on silica eluting with 0 to 3% tetrahydrofuran in ethyl acetate. The product was triturated in heptane to remove aliphatic impurities and then filtered and dried to afford Compound-59 (0.487 g) as a colorless solid. 1H-NMR (300 MHz, CDCl3) δ 7.14 (2H, m), 7.07 (1H, d), 6.95 (1H, m), 6.62 (1H, dd), 6.54 (1H, d), 4.38 (2H, t), 3.95 (2H, t), 3.06 (4H, m), 2.89 (2H, t), 2.66 (6H, m), 2.47 (2H, t), 1.90-1.65 (6H, m), 1.49-1.30 (6H, m), 0.88 (3H, t). [M+H]+=576.2.

1. waitAfter a further 10 minutes
2. waitThe reaction was held at −78° C. for 2 hours
3. temperatureto warm to room temperature overnight
4. customThe reaction was quenched with saturated aqueous ammonium chloride solution (30 mL)
5. extractionextracted with ethyl acetate (2×30 mL)
6. washwashed with saturated aqueous sodium hydrogen carbonate solution (30 mL), brine (30 mL)
7. dry with materialdried over MgSO4
8. concentrationconcentrated
9. customThe crude product was purified by column chromatography on silica eluting with 0 to 3% tetrahydrofuran in ethyl acetate
10. customThe product was triturated in heptane
11. customto remove aliphatic impurities
12. filtrationfiltered
13. customdried
14. customto afford Compound-59 (0.487 g) as a colorless solid