Quinolinyl ethers

The synthesis of 8-quinolinyl ethers from 8-hydroxyquinolines and organic halides has also recently been reported under PTC conditions with microwave irradiation (Eq. 18) [29]. 

Wang, J.X., Wang, C.H., Zhang, M., and Hu, Y. 1998. Synthesis of 8-quinolinyl ethers under microwave irradiation. Synthetic Communications, 28 2407-13. 

Leukotriene antagonist Tetrazolyl-2-quinolinyl methoxy aryl ethers 90JMC1186... 

To a solution of the N-methoxy-N-methyl-2,8-bis(trifluoromethyl)-quinoline-4-carboxamide amide (10 g, 28.4 mmol) in anhydrous ether (100 ml) was added a solution of 2-pyridyl lithium (Pinder et al (J. Med. Chem. 1968, 11, 267)) [formed by addition of 2-bromopyridine (3.3 ml, 34.6 mmol) to a solution of butyl lithium (29.7 ml of a commercial 1.6 M solution, diluted with an equal quantity of ether) at -78°C] at -78°C. Analysis of the reaction by TLC after 10 min showed that no starting material remained. The reaction was allowed to warm to room temperature, then poured into aqueous ammonium acetate, and extracted with ether, the combined organic layers washed with brine and dried (MgS04). Filtration through a pad of silica gel using ethyl acetate-hexane (1 1) afforded 9.0 g (84%) of the crude 2,8-bis(trifluoromethyl)-4-quinolinyl-2-pyridinylmethanone. This was recrystallised from isopropyl alcohol to give the product as colourless needles, identical to that described in the literature (Hickmann et al. Pinder et al. Ohnmacht et al. and Adam et al. (Tetrahedron 1991, 36, 7609)). 

A solution of benzo[/ ]quinolinyl chloro palladium acetate dimer (33.6 mg, 0.0444 mmol) in CH2CI2 (3 mL) was prepared at -50 °C. The solution was warmed to 23 °C. After stirring for 3 h at 23 °C, the solution was yellow. Solvent was removed in vacuo and the residue was purified by chromatography on silica gel eluting with hexanes/diethyl ether (9 1) to afford 8.9 mg of the title compound as a colorless solid (94%) Rf 0.32 (hexanes/Et20 9 1). ... 

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