Methane → N-[4-(3-Fluorobenzoyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

HRID 2259695노트

반응식

HRID 2259695 반응식
[F:1][C:2]([F:10])([F:9])[C:3]([OH:8])([CH3:7])[C:4](O)=[O:5].S(Cl)(Cl)=O.[NH2:15][C:16]1[CH:30]=[CH:29][C:19]([C:20]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=2)=[O:21])=[CH:18][CH:17]=1.C>CCCCCC.O>[F:28][C:24]1[CH:23]=[C:22]([C:20]([C:19]2[CH:18]=[CH:17][C:16]([NH:15][C:4](=[O:5])[C:3]([OH:8])([CH3:7])[C:2]([F:10])([F:9])[F:1])=[CH:30][CH:29]=2)=[O:21])[CH:27]=[CH:26][CH:25]=1

참가 물질

7

반응물 4

HCID 297MethaneHCID 24386Thionyl ChlorideHCID 27751253,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acidHCID 107987124-Amino-3'-fluorobenzophenone

생성물 1

HCID 10522137N-[4-(3-Fluorobenzoyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

시약·촉매·용매 2

HCID 962Water용매HCID 8058Hexane용매

실험 절차

To a stirred, cooled (-20° C.) solution of 3,3,3-trifiuoro-2-hydroxy-2-methylpropanoic acid (1.58 g, 10 mmol) in N,N-dimethylcetamide (15 mL) was added thionyl chloride (1.25 g, 10.5 mmol) and the mixture stirred at -20° to -10° C. for 1 hour. 4-Amino-3'-fluorobenzophenone (1.44 g, 6.7 mmol) was added in one portion and the reaction mixture stirred at room temperature overnight. The mixture was poured into water to yield an oil and a cloudy solution. The cloudy solution was decanted from the oil and filtered by suction through a pad of Celite. The Celite pad was washed with methylene chloride and the solution added to a solution of the gum in methylene chloride. The solution was dried (MgSO4), filtered and the solvent removed in vacuo. The resulting oil was chromatographed on silica gel (ethyl ether), the proper fractions combined and the solvent removed to yield an oil. The oil was dissolved in 50 mL of hexane containing enough methylene chloride to give a clear solution and the solution concentrated on a steambath until the solution became cloudy. The resulting pale yellow solid was collected by filtration and dried to yield 1.51 g (63%) of N-[4-(3-fluorophenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylproanamide, mp 121.5°-3° C. 1H-NMR (250 MHz, d6-DMSO): 1.59 (s, 3H, CH3) 3.32 (s, 1H, OH) 7.46-7.60 (m, 4H, aromatic) 7.75 (d, 2H, J=9.1 Hz aromatic) 7.96 (d, 2H, J=8.2 Hz, aromatic) 10.33 (s, 1H, NH). MS (CI, CH4): 356 (M+1). Analysis for C17H13F4NO3 : Calculated: C, 57.47; H, 3.69; N, 3.94; Found: C, 57.40; H, 3.65; N, 3.94;

후처리

  1. stirringthe reaction mixture stirred at room temperature overnight
  2. customto yield an oil
  3. customThe cloudy solution was decanted from the oil
  4. filtrationfiltered by suction through a pad of Celite
  5. washThe Celite pad was washed with methylene chloride
  6. additionthe solution added to a solution of the gum in methylene chloride
  7. dry with materialThe solution was dried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent removed in vacuo
  10. customThe resulting oil was chromatographed on silica gel (ethyl ether)
  11. customthe solvent removed
  12. customto yield an oil
  13. customto give a clear solution
  14. concentrationthe solution concentrated on a steambath until the solution
  15. filtrationThe resulting pale yellow solid was collected by filtration
  16. customdried
  17. customto yield 1.51 g (63%) of N-[4-(3-fluorophenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylproanamide, mp 121.5°-3° C

출처 및 근거

ORD 기록
ord-7150dc522d4848e096c826950d073108
출처 데이터셋
uspto-grants-1995_12
특허 번호
US05474999

반응 노트

불러오는 중…