Sodium hydride → 2-(2,5-Difluoro-4-nitrophenyl)-2-isobutylmalonic acid diethyl ester

HRID 385319

反応式

HRID 385319 の反応式
[CH2:1]([O:3][C:4](=[O:15])[CH:5]([CH2:11][CH:12]([CH3:14])[CH3:13])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2].[H-].[Na+].[F:18][C:19]1[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[C:22]([F:28])=[CH:21][C:20]=1F>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:15])[C:5]([C:20]1[CH:21]=[C:22]([F:28])[C:23]([N+:25]([O-:27])=[O:26])=[CH:24][C:19]=1[F:18])([CH2:11][CH:12]([CH3:13])[CH3:14])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 25047Diethyl isobutylmalonateHCID 750121,2,4-Trifluoro-5-nitrobenzene

生成物 1

HCID 579955742-(2,5-Difluoro-4-nitrophenyl)-2-isobutylmalonic acid diethyl ester収率 90.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒3 回

実験手順

2-Isobutylmalonic acid diethyl ester (40.0 g, 0.185 mol) in DMF (50 mL) was added dropwise to a stirred suspension of sodium hydride (60% in mineral oil, 8.0 g, 0.33 mol) in 200 mL DMF (200 mL) over 20 min. at 0° C. under nitrogen. The mixture was stirred for 0.5 h at room temperature, cooled to 0° C. and 1,2,4-trifluoro-5-nitro-benzene (30.0 g, 169.5 mmol) in DMF (150 mL) was added dropwise. The resulting reaction mixture was stirred at room temperature for 16 h, poured into ice water (200 mL) and extracted with EtOAc (3×100 mL). The combined organic phases were washed with water (3×100 mL), brine (100 mL) and dried (MgSO4). Evaporation of solvent under reduced pressure gave a brown oil which was purified by column chromatography over silica gel (Heptane-EtOAc, gradient) to give 57.0 g (90%) of 2-(2,5-difluoro-4-nitrophenyl)-2-isobutylmalonic acid diethyl ester as yellow oil. 1H NMR (300 MHz, CDCl3/TMS): δ 7.87 (dd, J=12.3, 6.0 Hz, 1H), 7.79 (dd, J=10.1, 6.4 Hz, 1H), 4.30-4.18 (m, 4H), 2.27 (d, J=5.8 Hz, 2H), 1.60-1.50 (m, 1H), 1.26 (t, J=7.1 Hz, 6H), 0.82 (d, J=7.0 Hz, 6H); 13C NMR (75 MHz, CDCl3/TMS): δ 168.2, 155.1 (d, 1JCF=252.3 Hz), 150.9 (d, 1JCF=263.2 Hz), 135.7, 135.1, 120.0 (dd, 2JCF=26.0, 3JCF=4.0 Hz), 113.0 (d, 2JCF=29.0 Hz), 62.3, 43.1, 24.9, 23.8, 13.8.

後処理

  1. temperaturecooled to 0° C.
  2. customThe resulting reaction mixture
  3. stirringwas stirred at room temperature for 16 h
  4. extractionextracted with EtOAc (3×100 mL)
  5. washThe combined organic phases were washed with water (3×100 mL), brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. customEvaporation of solvent under reduced pressure
  8. customgave a brown oil which
  9. customwas purified by column chromatography over silica gel (Heptane-EtOAc, gradient)

出典と根拠

ORDレコード
ord-dfda979c91ae43a9844ec70a555c1027
出典データセット
uspto-grants-2013_02
特許番号
US08367863B2

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