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

HRID 1467576Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1467576
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

Komponenten

4

Edukt 1

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

Produkt 1

HCID 575191766-Fluoro-4-nitro-2-benzofuran-1(3H)-oneAusbeute 79,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

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(3 H)-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)+.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-1bc3befa82a6407bbf43723e1c0727a3
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US08999987B2

Notizen zur Reaktion

Wird geladen…