Cesium carbonate → 4-benzyloxy-3-[(4-(N-methyl-N-(1-ethoxycarbonyl-1-methylethyl)amino)-3,5,6-trifluoropyridin-2-yl)oxy]benzonitrile

HRID 1066191노트

반응식

HRID 1066191 반응식
[CH3:1][N:2]([C:11]1[C:16]([F:17])=[C:15]([F:18])[N:14]=[C:13](F)[C:12]=1[F:20])[C:3]([C:6]([O:8][CH2:9][CH3:10])=[O:7])([CH3:5])[CH3:4].[CH2:21]([O:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]#[N:36])=[CH:31][C:30]=1[OH:37])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[OH-].[K+]>C(#N)C.C(OCC)(=O)C>[CH2:21]([O:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]#[N:36])=[CH:31][C:30]=1[O:37][C:13]1[C:12]([F:20])=[C:11]([N:2]([CH3:1])[C:3]([C:6]([O:8][CH2:9][CH3:10])=[O:7])([CH3:4])[CH3:5])[C:16]([F:17])=[C:15]([F:18])[N:14]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 14797Potassium HydroxideHCID 154534514-(Benzyloxy)-3-hydroxybenzonitrileHCID 211982104-[N-methyl-N-(1-ethoxycarbonyl-1-methylethyl)amino]-2,3,5,6-tetrafluoropyridine

생성물 1

HCID 211983374-benzyloxy-3-[(4-(N-methyl-N-(1-ethoxycarbonyl-1-methylethyl)amino)-3,5,6-trifluoropyridin-2-yl)oxy]benzonitrile수율 72.8%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 4-[N-methyl-N-(1-ethoxycarbonyl-1-methylethyl)amino]-2,3,5,6-tetrafluoropyridine (2.2 g, 6.6 mmol) in acetonitrile (60 mL) was added 2-benzyloxy-5-cyanophenol (1.5 g, 6.6 mmol) and cesium carbonate (2.8 g, 8.6 mmol). The resultant mixture was stirred at 40° C. for 2 days. The mixture was then cooled to ambient temperature and poured into 200 mL of 0.5 M aqueous KOH solution and 200 mL of ethyl acetate. The aqueous layer was separated and extracted with another 100 mL of ethyl acetate. The combined organic extracts were washed with 0.5 M aqueous KOH solution (200 mL) then brine (200 mL), dried over MgSO4, filtered, and concentrated in vacuo to afford a yellow oil which solidified upon standing. Recrystallization from 30% ethyl acetate/hexanes afforded 2.4 g (68% yield) of 4-benzyloxy-3-[(4-(N-methyl-N-(1-ethoxycarbonyl-1-methylethyl)amino)-3,5,6-trifluoropyridin-2-yl)oxy]benzonitrile as a white, crystalline solid: NMR (CDCl3) 7.6-7.1 (m, 8), 5.2 (s, 2), 4.2 (q, 2), 3.1 (s, 3), 1.6 (s, 6), 1.3 (t, 3) ppm.

후처리

  1. customThe aqueous layer was separated
  2. extractionextracted with another 100 mL of ethyl acetate
  3. washThe combined organic extracts were washed with 0.5 M aqueous KOH solution (200 mL)
  4. dry with materialbrine (200 mL), dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a yellow oil which
  8. customRecrystallization from 30% ethyl acetate/hexanes

출처 및 근거

ORD 기록
ord-3b44ecced05346478ba23e29b6b1825e
출처 데이터셋
uspto-grants-2001_06
특허 번호
US06242454B1

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