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

HRID 1814157

반응식

HRID 1814157 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
45 °C

실험 절차

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)

후처리

  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)

출처 및 근거

ORD 기록
ord-657285dbcfef488ca250b53152a3620b
출처 데이터셋
uspto-grants-2005_04
특허 번호
US06875780B2

연결된 노트

불러오는 중…