Cesium carbonate → 4-Benzyloxy-3-[(4-(methoxycarbonylmethyl)thio-3,5,6-trifluoropyridin-2-yl)oxy]benzonitrile

HRID 1636305Notes

Reaction equation

HRID 1636305 reaction equation
F[C:2]1[N:7]=[C:6]([F:8])[C:5]([F:9])=[C:4](F)[C:3]=1[F:11].[C:12]([O:16][CH3:17])(=[O:15])[CH2:13][SH:14].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:24]([O:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[CH:34][C:33]=1[OH:40])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[OH-].[K+]>C(#N)C.C(OCC)(=O)C>[CH2:24]([O:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[CH:34][C:33]=1[O:40][C:2]1[C:3]([F:11])=[C:4]([S:14][CH2:13][C:12]([O:16][CH3:17])=[O:15])[C:5]([F:9])=[C:6]([F:8])[N:7]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

8

Reactant 5

HCID 10796Cesium carbonate2×HCID 14797Potassium HydroxideHCID 16907Methyl ThioglycolateHCID 69690PentafluoropyridineHCID 154534514-(Benzyloxy)-3-hydroxybenzonitrile

Product 1

HCID 220017604-Benzyloxy-3-[(4-(methoxycarbonylmethyl)thio-3,5,6-trifluoropyridin-2-yl)oxy]benzonitrileYield 56.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of pentafluoropyridine (1.9 g, 11.2 mmol) in acetonitrile (25 mL) at 0° C. was added methyl thioglycolate (1.0 mL, 11.2 mmol) and cesium carbonate (4.4 g, 13.5 mmol). The resultant mixture was allowed to warm slowly to ambient temperature and stirred for 16 hours. To the mixture was added 2-benzyloxy-5-cyanophenol (2.6 g, 11.5 mmol) and cesium carbonate (4.4 g, 13.5 mmol). The resultant mixture was stirred at 40° C. for 16 hours. The mixture was then cooled to ambient temperature and poured into 150 mL of 0.5 M aqueous KOH solution and 150 mL of ethyl acetate. The organic layer was separated and washed further with 150 mL of 0.5 M aqueous KOH solution, then brine (150 mL), dried over MgSO4, filtered, and concentrated in vacuo to afford a yellow oil. Purification by flash chromatography on silica gel afforded 2.9 g (56% yield) of 4-benzyloxy-3-[(4-(methoxycarbonylmethyl)thio-3,5,6-trifluoropyridin-2-yl)oxy]benzonitrile, a compound of formula (E), as a pale yellow oil: NMR (CDCl3) 7.5-7.0 (m, 8), 5.1 (s, 2), 3.8 (s, 2), 3.7 (s, 3) ppm.

Workup

  1. temperatureThe mixture was then cooled to ambient temperature
  2. customThe organic layer was separated
  3. washwashed further with 150 mL of 0.5 M aqueous KOH solution
  4. dry with materialbrine (150 mL), dried 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-f3f7e66c3e684a4a957401d50349a38b
Source dataset
uspto-grants-2000_03
Patent number
US06034084

Reaction notes

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