Diethyl Oxalate → Ethyl 2,4-dioxo-4-[4-(trifluoromethyl)phenyl]butanoate

HRID 1814157

反応式

HRID 1814157 の反応式
[H-].[Na+].[F:3][C:4]([F:15])([F:14])[C:5]1[CH:10]=[CH:9][C:8]([C:11](=[O:13])[CH3:12])=[CH:7][CH:6]=1.[CH2:16]([O:18][C:19](=[O:25])[C:20](OCC)=[O:21])[CH3:17]>CN(C=O)C>[CH2:16]([O:18][C:19](=[O:25])[C:20](=[O:21])[CH2:12][C:11](=[O:13])[C:8]1[CH:7]=[CH:6][C:5]([C:4]([F:14])([F:15])[F:3])=[CH:10][CH:9]=1)[CH3:17]

参加物

5

反応物 3

HCID 7268Diethyl OxalateHCID 24758Sodium hydrideHCID 697311-(4-(Trifluoromethyl)phenyl)ethan-1-one

生成物 1

HCID 611940Ethyl 2,4-dioxo-4-[4-(trifluoromethyl)phenyl]butanoate収率 80%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
45 °C

実験手順

Sodium hydride (1.6 g, 63.7 mmol, 95%) was added to a solution of 1-(4-trifluoromethyl-phenyl)-ethanone (10.0 g, 53.1 mmol) and oxalic acid diethyl ester (8.7 mL, 63.7 mmol) in 75 mL dry DMF at 0° C. The reaction was allowed to come to room temperature and then heated to 45° C. for 45 minutes. The reaction was then cooled, concentrated in vacuo, and the residue taken up in EtOAc. The organic layer was then washed with 2 M HCl (1×100 mL), dried (Na2SO4) and the solvent removed in vacuo. Purification by flash column chromatography (gradient elution: 5% EtOAc/hexane to 55% EtOAc/hexane) gave the intermediate 2,4-dioxo-4-(4-trifluoromethyl-phenyl)-butyric acid ethyl ester (12.2 g, 80%) which was then taken up in EtOH and refluxed in the presence of hydroxylamine hydrochloride (10.2 g, 132.3 mmol) for 3H. The reaction was then cooled, diluted with EtOAc, washed with dilute NaHCO3, brine, dried (Na2SO4), and concentrated in vacuo. Recrystallization from EtOAc/hexane gave 5.2 g of the title compound. MS m/z 286 (M+1). Step 2. Preparation of [5-(4-Trifluoromethyl-phenyl)-isoxazol-3-yl]-methanol (Compound 13B)

後処理

  1. customto come to room temperature
  2. temperatureThe reaction was then cooled
  3. concentrationconcentrated in vacuo
  4. washThe organic layer was then washed with 2 M HCl (1×100 mL)
  5. dry with materialdried (Na2SO4)
  6. customthe solvent removed in vacuo
  7. customPurification
  8. washby flash column chromatography (gradient elution: 5% EtOAc/hexane to 55% EtOAc/hexane)

出典と根拠

ORDレコード
ord-657285dbcfef488ca250b53152a3620b
出典データセット
uspto-grants-2005_04
特許番号
US06875780B2

関連ノート

読み込み中…