Reacción #1605836

Ecuación de reacción

methylchloroformate

diisopropylamine

n-BuLi

aripiprazole

→

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

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
4. 4
   OtroAfter 2 hours the 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 1:1 ethyl acetate to dichloromethane to 10% methanol in 1:1 ethyl acetate to dichloromethane
10. 10
    Otroto give the product
11. 11
    OtroThe product was triturated in heptane
12. 12
    Otroto remove aliphatic impurities
13. 13
    Filtraciónfiltered
14. 14
    Otroto afford Compound-74 (0.824 g) as a colorless solid

Procedimiento

To a solution of diisopropylamine (0.99 mL, 7.02 mmol) in 2-methyltetrahydrfuran (33 mL) at −5° C. was added n-BuLi (2.67 mL, 2.5 M in hexanes, 6.69 mmol) slowly. After 20 minutes, the reaction was cooled to −78° C. and aripiprazole (1.50 g, 3.34 mmol) was added. After a further 10 minutes, methylchloroformate (0.65 mL, 8.36 mmol) was added. The reaction was held at −78° C. for 2 hours before allowing to warm to room temperature. After 2 hours 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 1:1 ethyl acetate to dichloromethane to 10% methanol in 1:1 ethyl acetate to dichloromethane to give the product. The product was triturated in heptane to remove aliphatic impurities and then filtered to afford Compound-74 (0.824 g) as a colorless solid.

Fuente