Reacción #1605831

Ecuación de reacción

hexylchloroformate

Aripiprazole

diisopropylamine

n-BuLi

→

Hexyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate

Disolventes

2-methyltetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.WAITAfter a further 10 minutes
2. 2
   workup.WAITThe reaction was held at −78° C. for 2 hours
3. 3
   Temperaturato warm to room temperature overnight
4. 4
   OtroThe reaction was quenched with saturated aqueous ammonium chloride solution (30 mL)
5. 5
   Extracciónextracted with ethyl acetate (2×30 mL)
6. 6
   Lavadowashed with saturated aqueous sodium hydrogen carbonate solution (30 mL), brine (30 mL)
7. 7
   Secadodried over MgSO4
8. 8
   Concentraciónconcentrated
9. 9
   OtroThe crude product was purified by column chromatography on silica eluting with 0 to 3% tetrahydrofuran in ethyl acetate
10. 10
    OtroThe product was triturated in heptane
11. 11
    Otroto remove aliphatic impurities
12. 12
    Filtraciónfiltered
13. 13
    Otrodried
14. 14
    Otroto afford Compound-59 (0.487 g) as a colorless solid

Procedimiento

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.

Fuente