Isopropyl iodide → 6-Amino-2-isopropoxy-4-trifluoromethylquinoline

In a 250-mL r.b. flask, a solution of 4-trifluoromethyl-6-nitroquinolinone (structure 1 of Scheme I) (3.78 g, 14.6 mmol) in DMF (75 mL) was treated with CsF (12.41 g, 73 mmol, 5.0 equiv.) and 2-iodopropane (11.09 g, 73 mmol, 5.0 equiv). The reaction mixture was stirred at room temperature (rt) for 18 h. The reaction mixture was quenched with H2O (100 mL) and extracted with EtOAc (3×200 mL). The combined EtOAc extracts were washed with saturated aqueous NH4Cl solution (300 mL), H2O (300 mL) and brine (300 mL). Dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash column chromatography (SiO2, 5×20 cm, 2% EtOAc in hexane as eluent) to afford 3.94 g (90%) of the 2-isopropoxyquinoline as a white solid. Rf 0.81 (SiO2, 10% EtOAc-hexane). 1H NMR (400 MHz, CDCl3) 8.93 (s, 1H), 8.47 (dd, 1H, J=9.2, 2.5) 7.98 (d, 1H, J=9.2), 7.32 (s, 1H), 5.62 (septet, 1H, J=6.2), 1.45 (d, 1H, J=6.2).

1. customThe reaction mixture was quenched with H2O (100 mL)
2. extractionextracted with EtOAc (3×200 mL)
3. washThe combined EtOAc extracts were washed with saturated aqueous NH4Cl solution (300 mL), H2O (300 mL) and brine (300 mL)
4. dry with materialDried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by flash column chromatography (SiO2, 5×20 cm, 2% EtOAc in hexane as eluent)

ORD record

ord-a7616f8f799147e8912a460d8754e812

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07026484B2