Reaction #1563949

Reaction equation

HBr

NaNO2

7-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-5-amine

HBr

→

5-bromo-7-fluoro-2,3-dihydrobenzo[b][1,4]dioxine

Solvents

water

Conditions

Workup

1. 1
   OtherReaction mixture
2. 2
   Otherwas quenched with ice water
3. 3
   Extractionextracted with ethyl acetate (3×50 mL)
4. 4
   Washwashed it with water
5. 5
   Dryingdried over anhydrous sodium sulphate
6. 6
   Concentrationconcentrated under reduced pressure
7. 7
   Otherto afford crude
8. 8
   OtherThe crude was purified by column purification (using silica gel and 0-5% ethyl acetate in Hexane as eluent)

Procedure

NaNO2 (2.69 g, 39.9 mmol) in water (20 mL) was added slowly at 0° C. to a solution of 7-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-5-amine (4.5 g, 26 mmol) in aq.47% HBr (20 mL) and continued stirring at same temperature for 30 min. The above diazonium salt solution was added slowly to a solution of CuBr (5.7 g, 39.9 mmol) in aq.47% HBr (25 mL) at 0° C. and stirred at 25° C. for 30 min. Reaction mixture was quenched with ice water, extracted with ethyl acetate (3×50 mL), washed it with water followed by brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford crude. The crude was purified by column purification (using silica gel and 0-5% ethyl acetate in Hexane as eluent) to afford 5-bromo-7-fluoro-2,3-dihydrobenzo[b][1,4]dioxine (Int-53) (5.9 g). 1H NMR (300 MHz, CDCl3) δ ppm 6.9-6.84 (1H, dd), 6.6-6.5 (1H, dd), 4.3-4.3 (4H, m).

Source