Methyl 2-(bromomethyl)-5-fluoro-2-methyl-3-nitrobenzoate → 6-Fluoro-4-nitro-2-benzofuran-1(3H)-one

HRID 907837Notes

Reaction equation

HRID 907837 reaction equation
BrC[C:3]1([CH3:17])[C:12]([N+:13]([O-:15])=[O:14])=[CH:11][C:10]([F:16])=[CH:9][CH:4]1[C:5]([O:7]C)=[O:6]>O1CCOCC1.O>[F:16][C:10]1[CH:9]=[C:4]2[C:3]([CH2:17][O:7][C:5]2=[O:6])=[C:12]([N+:13]([O-:15])=[O:14])[CH:11]=1

Participants

4

Reactant 1

HCID 67259110Methyl 2-(bromomethyl)-5-fluoro-2-methyl-3-nitrobenzoate

Product 1

HCID 575191766-Fluoro-4-nitro-2-benzofuran-1(3H)-oneYield 79.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl 5-fluoro-2-methyl-3-nitrobenzoate (28 g, 130.5 mmol), NBS (27.8 g, 156.6 mmol) and BPO (3.13 g, 13.1 mmol) in CCl4 (400 mL) was heated to reflux overnight. TLC (petroleum ether/EtOAc=15:1) showed the starting material was consumed completely. Water (200 mL) was added and CCl4 was removed under reduced pressure. The residue was extracted with DCM (200 mL×3). The combined organic layers were washed with brine, dried over Na2SO4, concentrated to give crude methyl 2-(bromomethyl)-5-fluoro-2-methyl-3-nitrobenzoate (36 g, yield 94%) as a brown oil. A mixture of methyl 2-(bromomethyl)-5-fluoro-2-methyl-3-nitrobenzoate (36 g, 123 mmol) in 1,4-dioxane (250 mL) and water (62.5 mL) was heated to reflux for 4 days. TLC (petroleum ether/EtOAc=15:1) showed the starting material was consumed completely. Dioxane was removed under reduced pressure. The residue was extracted with EtOAc (300 mL×4). The combined organic layers were washed with brine, dried over Na2SO4, concentrated to give crude product. The crude product was purified by gel chromatography (petroleum ether to petroleum ether/EtOAc=5:1) to give 6-fluoro-4-nitroisobenzofuran-1(3H)-one (19.2 g, yield 79%) as a white solid. 1H-NMR (400 MHz, CDCl3) δ (ppm): 5.74 (s, 2H), 7.97-7.98 (dd, 1H), 8.24-8.27 (dd, 1H); LC-MS (ESI) m/z: 198(M+1)+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 4 days
  3. customwas consumed completely
  4. customDioxane was removed under reduced pressure
  5. extractionThe residue was extracted with EtOAc (300 mL×4)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customto give crude product
  10. customThe crude product was purified by gel chromatography (petroleum ether to petroleum ether/EtOAc=5:1)

Sources & evidence

ORD record
ord-789b73849e7d4daa9607d7f5f8144e23
Source dataset
uspto-grants-2011_09
Patent number
US08012976B2

Reaction notes

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