Reaction #710571

Reaction equation

Ethyl iodide

2-bromopropane

2-methylquinaldine

K2CO3

→

8-ethoxy-2-methylquinoline

Solvents

DMF

Conditions

Workup

1. 1
   OtherThe reaction mixture was quenched by H2O (200 ml)
2. 2
   Extractionextracted with EtOAc (50 ml×2)
3. 3
   ConcentrationThe organic layer was concentrated by evaporation in vacuum
4. 4
   OtherThe residue was purified by flash column chromatography with Hex/EA (6:1)
5. 5
   Otherrecrystallized with Hexane/EA

Procedure

Ethyl iodide (3.9 g, 25.0 mmol) or 2-bromopropane (2.4 g, 19.2 mmol) was added to a stirred solution of 2-methylquinaldine (3.0 g, 18.8 mmol) and K2CO3 (6.5 g 47 mmol; 5.2 g, 37.6 mmol) in 30 ml DMF at 60° C. for 14 h. The reaction mixture was quenched by H2O (200 ml) and extracted with EtOAc (50 ml×2). The organic layer was concentrated by evaporation in vacuum. The residue was purified by flash column chromatography with Hex/EA (6:1) and recrystallized with Hexane/EA to give 8-ethoxy-2-methylquinoline as intermediate (2.75 g, 78%) in solid but liquid form for 8-isopropopxy-2-methylquinoline (2.92 g, 77%). LHMDS (2.2 equiv.) was treated with a stirred solution of different intermediates in THF solution at 0° C. for 1 h. Corresponding Br(CH2)n−1OH (1.1-1.2 equiv.) was added to a reaction mixture and recover to RT for further 12 to 30 h. The solvent was removed under a reduced pressure. The brown oily residue was purified by flash column chromatography with Hex/EA or DCM/BA and recrystallized by Hexane/EA to afford compound D and E.

Source