Sodium hydride → Diethyl 2-fluoro-2-phenylmalonate

HRID 1633207

反応式

HRID 1633207 の反応式
[C:1]1([CH:7]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[H][H].[F:22]N(CC(C)(C)C)S(C1C=CC(C)=CC=1)(=O)=O>O1CCCC1.CCOCC>[F:22][C:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:13]([O:15][CH2:16][CH3:17])=[O:14]

参加物

7

反応物 4

HCID 24758Sodium hydrideHCID 66514Diethyl phenylmalonateHCID 145159p-Tolyl-N-fluoro-N-neopentylsulfonamideHCID 178418361HCID 178418361、化合物

生成物 1

HCID 4246642Diethyl 2-fluoro-2-phenylmalonate収率 81%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

Diethyl phenylmalonate (472 mg, 431 μL, 2 mmole) was dissolved in anhydrous tetrahydrofuran (10 mL) under nitrogen. Sodium hydride (96 mg as a 60% oil dispersion, 2.4 mmole) was added and the mixture was stirred until hydrogen evolution ceased (about 15 minutes). The solution was then cooled to -50° under nitrogen and N-fluoro-N-neopentyl-p-toluenesulfonamide (518 mg, 2 mmole, as prepared in Example 1) was added and the mixture was stirred at -50° for 15 minutes. The solution was stirred at -20° for 15 minutes, 0° for 15 minutes, and room temperature for 15 minutes before being diluted with ether (100 mL). The ether solution was washed with aqueous 1N oxalic acid (30 mL), 10% aqueous potassium bicarbonate (30 mL), and saturated aqueous sodium chloride (30 mL) solutions, and then dried over anhydrous magnesium sulfate. Filtration, removal of solvent under reduced pressure, and purification by flash column chromatography (silica, 30% methylene chloride in hexane) yielded diethyl 2-fluoro-2-phenylmalonate (410 mg, 81% yield) as a colorless oil. This material, and additional samples prepared by this procedure, were analyzed and provided the following results: IR (liquid film) γmax (cm-1) 2800 (m), 1760 (s, ester), 1420 (m), 1350 (m), 1250 (s); 1H NMR (80 MHz, CDCl3) δ1.32 (t, J=8.0 Hz, 6H, CH3), 4.33 (q, J=8 Hz, 4H, CH2), 7.50 (m, 5H); 19F NMR (94.1 MHz, CDCl3) -162.23; HRMS calcd. for C13H15O4F: 254.0954; found: 254.0947.

後処理

  1. custom(about 15 minutes)
  2. temperatureThe solution was then cooled to -50° under nitrogen
  3. stirringThe solution was stirred at -20° for 15 minutes, 0° for 15 minutes
  4. washThe ether solution was washed with aqueous 1N oxalic acid (30 mL), 10% aqueous potassium bicarbonate (30 mL), and saturated aqueous sodium chloride (30 mL) solutions
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationFiltration, removal of solvent
  7. customunder reduced pressure, and purification by flash column chromatography (silica, 30% methylene chloride in hexane)

出典と根拠

ORDレコード
ord-4a6441a75a774b1481958124ad1082a3
出典データセット
uspto-grants-1984_10
特許番号
US04479901

関連ノート

読み込み中…