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3.2. General Procedure for the Synthesis of 6-Methoxy-2-Methylquinolines
6-Methoxy-2-methylquinolin-4-ol ( ) (1 mmol), benzyl bromides ( ) (1.2 mmol), and K2CO3
1
2
(0.415 g, 3 mmol) were mixed in DMF (20 mL) in a 100 mL beaker. The reaction mixture
was sonicated for 15 min using an ultrasonic probe. Afterwards, the amount of solvent
was decreased under reduced pressure, and the resultant mixture was diluted in water.
Subsequently, the solid formed was filtered off and washed under agitation with water
(
3 × 20 mL); after each wash, the product was separated from the liquid phase by centrifu-
◦
gation (10 min, 18,000 rpm at 4 C). Finally, the product was dried under reduced pressure
for at least 24 h. Analytical data were found to be in agreement with the already reported
data [9]. Compounds 3a and 3b were selected for exemplification.
4-(Benzyloxy)-6-methoxy-2-methylquinoline (3a): yield 84%; white to slightly yellow
solid; m.p.: 140–141 ◦C; HPLC 95% (tR = 14.57 min); 1H NMR (400 MHz, DMSO-d6)
δ 2.55
(s, 3H, CH3), 3.84 (s, 3H, CH3), 5.38 (s, 2H, CH2), 7.00 (s, 1H, Qu-H*), 7.40–7.30 (m, 3H,
Qu-H*, Ph-H), 7.49–7.41 (m, 2H, Ph-H), 7.58 (dt, J = 6.3, 1.4 Hz, 2H, Qu-H*, Ph-H), 7.79 (d,
J = 9.1 Hz, 1H, Qu-H*); HRMS (FTMS + pESI) m/z calcd. for C18H17NO2 (M)+: 280.1332;
found: 280.1325; Qu-H*: quinolines hydrogens.
4-((4-Fluorobenzyl)oxy)-6-methoxy-2-methylquinoline (3b): yield 62%; white solid;
mp.: 114–115 ◦C; HPLC 95% (tR = 15.12 min); 1H NMR (400 MHz, DMSO-d6)
δ 2.59 (s, 3H,
CH3), 3.84 (s, 3H, CH3), 5.35 (s, 2H, CH2), 6.98 (s, 1H, Qu-H*), 7.40–7.25 (m, 4H, Ph-H, Qu-
H*), 7.69–7.58 (m, 2H, Ph-H, Qu-H*), 7.81 (d, J = 9.0 Hz, 1H, Qu-H*); HRMS (FTMS + pESI)
m/z calcd. for C18H16FNO2 (M)+: 298.1238; found: 298.1245; Qu-H*: quinolines hydrogens.
Author Contributions: A.F.B. and J.D.P. are equal-contributing first authors. Writing—Original Draft
Preparation: A.F.B., J.D.P., K.P., R.S.R., V.Z.P., C.V.B., L.A.B. and P.M. Writing—Review and Editing:
P.M. All authors have read and agreed to the published version of the manuscript.
Funding: This research was funded by CNPq/FAPERGS/CAPES/BNDES, Brazil (grant numbers:
421703-2017-2/17-1265-8/14.2.0914.1) to C.V.B., L.A.B. and P.M. In addition, this study was financed
in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES),
Finance Code 001. C.V.B., L.A.B. and P.M. are Research Career Awardees of the National Research
Council of Brazil (CNPq). Fellowships from CNPq (R.S.R. and V.Z.P.) and CAPES (J.D.P. and A.F.B.)
are also acknowledged.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.
Sample Availability: Samples of the synthesized compounds are available from the authors.
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