Reaction #40348

Reaction equation

4-trifluoromethyl-6-nitroquinolinone

CsF

2-iodopropane

→

2-isopropoxyquinoline

Yield 99.9%

6-Amino-2-isopropoxy-4-trifluoromethylquinoline

Yield 99.9%

Solvents

DMF

Conditions

Workup

1. 1
   OtherThe reaction mixture was quenched with H2O (100 mL)
2. 2
   Extractionextracted with EtOAc (3×200 mL)
3. 3
   WashThe combined EtOAc extracts were washed with saturated aqueous NH4Cl solution (300 mL), H2O (300 mL) and brine (300 mL)
4. 4
   DryingDried (MgSO4)
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated in vacuo
7. 7
   OtherThe residue was purified by flash column chromatography (SiO2, 5×20 cm, 2% EtOAc in hexane as eluent)

Procedure

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).

Source