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

HRID 324992

Reaction equation

HRID 324992 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-55d63ad679ef40f896e7fd7627d542ae
Source dataset
uspto-grants-2001_04
Patent number
US06221886B1

Linked notes

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