Water → 4-benzyloxy-3-[(4-(N-methyl-N-(1-ethoxycarbonylcyclopent-1-yl)amino)-3,5,6-trifluoropyridin-2-yl)oxy]benzonitrile

HRID 613400Notes

Reaction equation

HRID 613400 reaction equation
[CH3:1][N:2]([C:13]1[C:18]([F:19])=[C:17](F)[N:16]=[C:15]([F:21])[C:14]=1[F:22])[C:3]1([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4]1.[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]#[N:38])=[CH:33][C:32]=1[OH:39])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>C(#N)C.C(OCC)(=O)C>[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]#[N:38])=[CH:33][C:32]=1[O:39][C:17]1[C:18]([F:19])=[C:13]([N:2]([CH3:1])[C:3]2([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4]2)[C:14]([F:22])=[C:15]([F:21])[N:16]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 154534514-(Benzyloxy)-3-hydroxybenzonitrileHCID 154632514-(N-methyl-N-(1-ethoxycarbonylcyclopent-1-yl)amino)-2,3,5,6-tetrafluoropyridine

Product 1

HCID 154632524-benzyloxy-3-[(4-(N-methyl-N-(1-ethoxycarbonylcyclopent-1-yl)amino)-3,5,6-trifluoropyridin-2-yl)oxy]benzonitrileYield 60%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(N-methyl-N-(1-ethoxycarbonylcyclopent-1-yl)amino)-2,3,5,6-tetrafluoropyridine (0.89 g, 2.8 mmol) in acetonitrile (30 mL) was added 2-benzyloxy-5-cyanophenol (0.63 g, 2.8 mmol) and cesium carbonate (1.2 g, 3.6 mmol). The resultant mixture was stirred at 60° C. for 1 day. The mixture was then cooled to ambient temperature and poured into 100 mL of water and 100 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 1 M aqueous KOH solution (100 mL), brine (100 mL), dried over MgSO4, filtered, and concentrated in vacuo to afford a yellow oil. Purification by flash chromatography on silica gel afforded 0.87 g (60% yield) of 4-benzyloxy-3-[(4-(N-methyl-N-(1-ethoxycarbonylcyclopent-1-yl)amino)-3,5,6-trifluoropyridin-2-yl)oxy]benzonitrile, a compound of formula (G), as a clear, colorless oil: NMR (CDCl3) 7.6-7.1 (m, 8), 5.2 (s, 2), 4.2 (q, 2), 3.1 (s, 3), 2.3-1.6 (m, 8), 1.3 (t, 3) ppm.

Workup

  1. customThe aqueous layer was separated
  2. extractionextracted with another 100 mL of ethyl acetate
  3. washThe combined organic extracts were washed with 1 M aqueous KOH solution (100 mL), brine (100 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a yellow oil
  8. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-49c4696e0ea04ef685e041eb128caf1f
Source dataset
uspto-grants-1999_12
Patent number
US06008234

Reaction notes

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