Hydrogen Bromide → 1-(2-Fluoro-3-hydroxy-6-nitrophenyl)propan-2-one

HRID 585789Notes

Reaction equation

HRID 585789 reaction equation
C([O:8][C:9]1[C:10]([F:22])=[C:11]([CH2:18][C:19](=[O:21])[CH3:20])[C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=1)C1C=CC=CC=1.Br>C(OC(=O)C)(=O)C.C(O)(=O)C>[F:22][C:10]1[C:9]([OH:8])=[CH:14][CH:13]=[C:12]([N+:15]([O-:17])=[O:16])[C:11]=1[CH2:18][C:19](=[O:21])[CH3:20]

Participants

5

Reactant 2

HCID 260Hydrogen BromideHCID 112896631-[3-(Benzyloxy)-2-fluoro-6-nitrophenyl]propan-2-one

Product 1

HCID 223379951-(2-Fluoro-3-hydroxy-6-nitrophenyl)propan-2-oneYield 80%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 7918Acetic AnhydrideSolvent

Conditions

Temperature
100 °C

Procedure

Method G-1: To a solution of 1-(3-benzyloxy-2-fluoro-6-nitrophenyl)-propan-2-one (3.03 g, 10 mmol) in acetic anhydride (5 mL) and acetic acid (5 mL) at room temperature was added hydrobromic acid (48% aqueous solution, 3 mL). After addition, the reaction was heated at 100° C. for 30 min and then cooled to room temperature. To this mixture was added 10 mL of hexanes with stirring. The solution was decanted and concentrated. The residue was diluted with ethyl acetate (50 mL) and washed with brine (3×20 mL). The organic layer was dried and concentrated in vacuo to provide 1-(2-fluoro-3-hydroxy-6-nitrophenyl)-propan-2-one (1.7 g, 80%) as a brown solid, which was used in the next step without further purification. LC/MS; (M+H)+=213.2 Method G-2: A mixture of 1-(3-benzyloxy-2-fluoro-6-nitrophenyl)-propan-2-one (65.0 g, 0.214 mol) and pyridinium chloride (60.74 g, 0.526 mol) was stirred at 180° C. for 1 hr. The reaction mixture was cooled to room temperature, diluted with 3N HCl (100 mL) and ethyl acetate (500 mL) and filtered. The aqueous layer was extracted with ethyl acetate (2×) and the combined organic layers were washed with brine, dried (MgSO4),s filtered through a pad of silica gel and concentrated in vacuo. The residue was decolorized with charcoal in methanol, filtered and concentrated in vacuo to afford 1-(2-fluoro-3-hydroxy-6-nitrophenyl)-propan-2-one (37 g, 81%) as a brown solid. LC/MS; (M+H)+=213.2

Workup

  1. additionAfter addition
  2. temperaturecooled to room temperature
  3. customThe solution was decanted
  4. concentrationconcentrated
  5. additionThe residue was diluted with ethyl acetate (50 mL)
  6. washwashed with brine (3×20 mL)
  7. customThe organic layer was dried
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a76c19eb3e1545aa8de114ff0577f189
Source dataset
uspto-grants-2005_08
Patent number
US06933386B2

Reaction notes

Loading…