6-bromo-7-methylquinoline synthesis

Yield: 31%

Reaction Conditions:

Stage #1:amino-5-bromo-2-toluene;glycerol with iron(III) sulfate;sulfuric acid in nitrobenzene for 3 h;Heating / reflux;
Stage #2: with water;sodium hydrogencarbonate in nitrobenzene; pH=7 - 8

Steps:

1.4
Intermediate 4: 6-Bromo-7-methyl-quinoline; [0304] A mixture of 4-bromo-3-methylaniline (20 g, 107.5 mmol), ferric sulfate (6.6 g, 43.4 mmol), glycerol (40.8 g, 440 mmol), nitrobenzene (8.12 g, 66 mmol), and concentrated EPO sulfuric acid (23 ml) was heated gently. After the first vigorous reaction, the mixture was boiled for 3h and then evaporated to remove the excess nitrobenzene. The solution was added a saturated aqueous solution of sodium bicarbonate until pH=7-8, then the solution was filtered and extracted with dichloromethane. The combined organic layers were dried over Na₂SO₄, filtered and concentrated in vacuo. The solid was purified by flash column chromatography to give a yellow solid, which was further washed with petroleum ether to give 7.5 g of 6-bromo-7-methyl-quinoline (31% yield): ¹H NMR (CDCl₃): 2.60 (s, 3H), 7.36 (m, IH), 7.96 (s, IH), 8.04 (m, 2H), 8.89 (m, IH).

References:

SGX PHARMACEUTICALS, INC. WO2008/51808, 2008, A2 Location in patent:Page/Page column 79-80