Hydrochloric Acid → 3-Bromo-4-fluoroaniline

Participants

Reaction Conditions

Reaction Steps

Sodium chlorite (6.78 g, 75 mmol) and 4-fluoro-3-bromobenzaldehyde (24.63 mmol) were dissolved in 1:1 THF/water (100 mL) and stirred vigorously at 50° C. for 5 h. EtOAc (250 mL) and 1N HCl (50 mL) was added and the layers were separated. The organic layer was washed with water (3×50 mL), then was extracted with 0.5M Na2CO3 (10×50 mL). The combined basic aqueous layers were slowly acidified with concentrated HCl while stirring, to precipitate the carboxylic acid product. The solid was collected via filtration and dried under high vacuum overnight (4.93 g, 91%). A portion of the solid carboxylic acid was dissolved in chloroform (30 mL) and concentrated sulfuric acid was added. A reflux condenser was attached to the flask and the solution was heated to 55° C. Sodium azide (2.36 g, 36.45 mmol) was added in 3 portions over 1 h. After 4 h, additional sulfuric acid (10 mL) and sodium azide (1 g) were added and the reaction was stirred at 55° C. for 16 h. The mixture was transferred to a large cooled flask and the sulfuric acid was slowly quenched with 5N sodium hydroxide. The solution was adjusted to pH˜8 and the aqueous solution was extracted with DCM (5×30 mL). The organic extracts were dried over sodium sulfate and concentrated in vacuo to yield a dark brown oil (2.2 g, 95%) that solidified upon standing. 1H-NMR (CDCl3): δ 6.94 (t, 8.4 Hz), 6.88 (dd, 1H, J=2.8, 5.6 Hz), 6.58 (m, 1H), 3.62 (s, 2H).

Provenance & Evidence