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

HRID 907837ノート

反応式

HRID 907837 の反応式
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

参加物

4

反応物 1

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-789b73849e7d4daa9607d7f5f8144e23
出典データセット
uspto-grants-2011_09
特許番号
US08012976B2

反応ノート

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