General procedure for the synthesis of 6-hydroxymethylquinoline from methyl 6-quinolinecarboxylate: cooling of a 0.2 M solution of methyl 6-quinolinecarboxylate (0.300 g, 1.60 mmol) in THF (8 mL) and a 0.6 M solution of diisobutylaluminum hydride (DIBAL) (0.860 mL, 4.81 mmol) in THF in an acetone-dry ice bath at -78 °C ( 8mL). The DIBAL solution was transferred to the methyl ester solution via cannula and the resulting solution was stirred for 1 h at 0 °C. The reaction was quenched by the addition of methanol (8 mL) and acetic acid (1.37 mL, 24.0 mmol) at 0 °C. After stirring for 5 min, saturated sodium tartrate solution (16 mL) was added. Stirring was continued for 20 min, followed by dilution of the reaction mixture with EtOAc (50 mL) and water (10 mL). The aqueous layer was extracted with EtOAc (3 x 50 mL). The organic phases were combined and washed once with 15 mL of water. The organic layer was dried with Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (50-90% EtOAc/hexane) afforded 0.236 g (93%) of 6-hydroxymethylquinoline (S3a) as a pale yellow oil.1H NMR (500 MHz, CDCl3): δ 4.89 (s, 2H), 7.35 (dd, 1H, J=4.0,8.0), 7.65 (dd, 1H, J=1.5, 9.0), 7.77 (s, 1H), 8.01 (d, 1H, J=9.0), 8.08 (d, 1H, J=4.0), 8.80 (dd, 1H, J=1.5,4.0).13C-NMR (125MHz, CDCl3): δ64.8,121.5,125.0,128.3,129.0,129.4. 136.4,139.9,147.7,150.2. HRMS-FAB (m/z): calculated value for [MH]+ C10H10NO, 160.0762; measured value: 160.0766.
