Hydrogen Bromide → 5-Bromo-7-fluoro-2,3-dihydrobenzo[b][1,4]dioxine

HRID 2167733Notes

Reaction equation

HRID 2167733 reaction equation
N([O-])=O.[Na+].[F:5][C:6]1[CH:7]=[C:8](N)[C:9]2[O:14][CH2:13][CH2:12][O:11][C:10]=2[CH:15]=1.[BrH:17]>O>[Br:17][C:8]1[C:9]2[O:14][CH2:13][CH2:12][O:11][C:10]=2[CH:15]=[C:6]([F:5])[CH:7]=1

Participants

5

Reactant 3

HCID 260Hydrogen Bromide2×HCID 23668193Sodium NitriteHCID 666806007-Fluoro-2,3-dihydro-1,4-benzodioxin-5-amine

Product 1

HCID 896359545-Bromo-7-fluoro-2,3-dihydrobenzo[b][1,4]dioxine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

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).

Workup

  1. stirringstirred at 25° C. for 30 min
  2. customReaction mixture
  3. customwas quenched with ice water
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. washwashed it with water
  6. dry with materialdried over anhydrous sodium sulphate
  7. concentrationconcentrated under reduced pressure
  8. customto afford crude
  9. customThe crude was purified by column purification (using silica gel and 0-5% ethyl acetate in Hexane as eluent)

Sources & evidence

ORD record
ord-67cf7bdaec3f42c5bb27e79f7993db2c
Source dataset
uspto-grants-2015_06
Patent number
US09045478B2

Reaction notes

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