Dimethyl malonate → HCID 10322194、化合物

HRID 275479

反応式

HRID 275479 の反応式
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[H-].[Na+].Br[CH2:13][C:14]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)=[O:15].Br[CH2:24][C:25]([C:27]1[CH:32]=[CH:31][C:30]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:29][CH:28]=1)=[O:26]>CN(C=O)C>[CH3:6][O:5][C:3](=[O:4])[C:2]([CH2:13][C:14]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)=[O:15])([CH2:24][C:25]([C:27]1[CH:28]=[CH:29][C:30]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:31][CH:32]=1)=[O:26])[C:1]([O:8][CH3:9])=[O:7]

参加物

6

反応物 4

HCID 7943Dimethyl malonateHCID 24758Sodium hydride2 回HCID 967492-Bromo-1-(4-fluorophenyl)ethan-1-oneHCID 7358232-Bromo-4'-(methylsulfonyl)acetophenone

生成物 1

HCID 10322194HCID 10322194、化合物収率 51%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 7.18 mL (63 mmol) of dimethyl malonate in 160 mL of DMF at 0° C. under an atmosphere of nitrogen was added 3.0 g (75 mmol) of sodium hydride (60% suspension in oil). The reaction was stirred at ambient temperature for 15 minutes (or until the gas evolution has ceased), cooled to -20° C., and treated with 15 g (69 mmol) of 2-bromo-4'-fluoroacetophenone (Aldrich) in one portion. The mixture was stirred at ambient temperature for 1 hour and then cooled to 0° C.; another 75 mmol of sodium hydride was added and the resulting mixture stirred at ambient temperature for 15 minutes (or until the gas evolution has ceased). The reaction was recooled to -20° C. and treated with 19.1 g (69 mmol) of 2-bromo-4'-(methylsulfonyl)acetophenone (prepared in Step 3). The reaction was stirred at room temperature for 2 hours and concentrated in vacuo. The residue was partitioned between water and ethyl acetate; the ethyl acetate phase was dried (MgSO4) and reconcentrated in vacuo. The residue was chromatographed on silica gel to give 13.8 g (51%) of dimethyl2-[2-(4-fluorophenyl)-2-oxoethyl]-2-[2-[4-(methylsulfonyl)phenyl]-2-oxoethyl]propanedioate as an oil: NMR (CDCl3) δ 3.06 (s, 3H), 3.76 (s, 6H), 4.03 (s, 2H), 4.08 (s, 2H), 7.13 (t, J=8.6 Hz, 2H), 7.97-8.05[m with d at 8.03 (J=8.7 Hz), 4H], 8.14 (d, J=8.5 Hz, 2H).

後処理

  1. temperaturecooled to -20° C.
  2. stirringThe mixture was stirred at ambient temperature for 1 hour
  3. temperaturecooled to 0° C.
  4. stirringthe resulting mixture stirred at ambient temperature for 15 minutes (or until the gas evolution
  5. customwas recooled to -20° C.
  6. stirringThe reaction was stirred at room temperature for 2 hours
  7. concentrationconcentrated in vacuo
  8. customThe residue was partitioned between water and ethyl acetate
  9. dry with materialthe ethyl acetate phase was dried (MgSO4)
  10. customThe residue was chromatographed on silica gel

出典と根拠

ORDレコード
ord-b74f8b3bdbaa492bae283f54b6f4cad1
出典データセット
uspto-grants-1995_02
特許番号
US05393790

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