79.1% |
With sodium hydride; In tetrahydrofuran; mineral oil; for 2h; |
5-Bromo-1,6-dimethyl-1H-indole (FJG. 2, compound 2) was synthesized as follows. A flame-dried round-bottom flask was charged with compound 14 (5.41 g, 25.8 mmol, 1.0 eq., FJG. 2) and anhydrous THF (50 mL). The solution was cooled in an ice-bath and treated with NaH as a 60%dispersion in mineral oil (1.24 g, 30.9 mmol, 1.2 eq.) and methyl iodide (3.2 mL, 51.5 mmol, 2.0 eq.). After stirring at 0 C for 2 hrs, the volatiles were removed under reduced pressure. The residue was dissolved with CH2C12 (100 mL) and washed with brine (50 mL). The organic fraction was (Na2SO4), filtered and concentrated to afford the crude product which was purified via flash chromatography on a silica column (7:193 v/v EtOAc:Hexanes) to afford the title compound as a yellow solid (4.56 g, 20.3 mmol, 79.1% yield). ?H NMR (500 MHz, Acetone-d6) 10.27 (bs, NH), 7.82 (s, 1H), 7.41 (s, 1H), 7.31 (dd, J= 3.2, 2.4 Hz, 1H), 6.45 (td, J= 2.1, 1.0 Hz, 1H), 2.48 (d, J= 0.8 Hz, 3H). ?3C NMR (125 MHz, Acetone-d6) 136.1, 129.7, 128.5, 126.0, 123.5, 115.6, 113.2, 101.1, 23.1. m.p. = 90-91 C. JR (neat):33143118, 3095, 1467, 1338 1753, 1705, 1614, 1507, 1468, 1270, 993, 881, 842, 730, 693, 606 cm?. HR-MS calculated for C,0H,0BrN [M+H] m/z 224.0075, found 224.0079. |