Quinoline → 4-Bromobenzo[b]thiophene

Participants

Reaction Conditions

Reaction Steps

Copper powder (49.8 g) is added to a stirred mixture of 4-bromo-benzo[b]thiophene-2-carboxylic acid (995.5 g, 3.87 mol) and quinoline (1.99 L) and the resultant mixture is heated to and maintained at 15 to 195° C. for 5 h. The mixture is allowed to cool to room temperature and the reaction is quenched by the addition of a mixture of ice (5.81 Kg) and concentrated hydrochloric acid (2.48 L). TBME (9 L) is added and the mixture is stirred vigorously for 10 min and filtered. The clarified layers are separated and the aqueous layer is extracted with TBME (1.0 L). The combined extracts are washed with hydrochloric acid (1 M, 2×5.00 L) and water (4.0 L), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to afford the crude product (640 g) as a brown oil which solidifies on standing overnight. The residue is slurried in methanol (500 mL, 0.5 vol) at −10 to 0° C. for 1.5 h, the observed solid material is collected by filtration and pulled dry on the filter. The methanolic mother liquors are concentrated by rotary evaporation. The residue is combined with the isolated solid material, slurried in TBME (2.0 L) and the collected solids are washed with TBME (660 L). The combined liquors and washes are washed with hydrochloric acid (1 M, 660 mL), saturated aqueous sodium hydrogen carbonate. (2×1.0 L) and water (4.0 L), dried over magnesium sulfate, filtered and concentrated by rotary evaporation at 40° C. to afford the crude product. The residue is slurried in methanol (1.10 L) at −10 to 0° C. for 1 h. The observed solid is collected by filtration and dried under vacuum at 20° C. to afford 4-bromo-benzo[b]thiophene as an off-white solid (315 g, 37%). 1H NMR (CDCl3): δ 7.81 (d, 1H, J=8.0 Hz), 7.57-7.48 (m, 3H), 7.21 (t, 1H, J=7.7 Hz).

Provenance & Evidence