18-Crown-6 → 3-[(6-Chloro-2-fluoro-3-methylphenyl)oxy]-5-(trifluoromethyl)benzonitrile

HRID 1875137Notes

Reaction equation

HRID 1875137 reaction equation
[Cl:1][C:2]1[C:7]([OH:8])=[C:6]([F:9])[C:5]([CH3:10])=[CH:4][CH:3]=1.C1OCCOCCOCCOCCOCCOC1.CC(C)([O-])C.[K+].F[C:36]1[CH:37]=[C:38]([CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=1)[C:39]#[N:40]>CS(C)=O.O>[Cl:1][C:2]1[C:7]([O:8][C:36]2[CH:37]=[C:38]([CH:41]=[C:42]([C:44]([F:45])([F:47])[F:46])[CH:43]=2)[C:39]#[N:40])=[C:6]([F:9])[C:5]([CH3:10])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 2855718-Crown-6HCID 5190373-Fluoro-5-(trifluoromethyl)benzonitrileHCID 27736846-Chloro-2-fluoro-3-methylphenolHCID 23665647Potassium tert-butoxide

Product 1

HCID 684874043-[(6-Chloro-2-fluoro-3-methylphenyl)oxy]-5-(trifluoromethyl)benzonitrileYield 72.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a solution of 6-chloro-2-fluoro-3-methylphenol (8.49 g, 52.9 mmol) and 18-crown-6 (13.98 g, 52.9 mmol) in dimethyl sulfoxide (80 ml) was added potassium t-butoxide (20% wt solution in THF) (31.2 g, 55.5 mmol) (31.2 mL) and the mixture was stirred at rt for 30 minutes. Next, 3-fluoro-5-(trifluoromethyl)benzonitrile (10.00 g, 52.9 mmol) was added and the mixture was heated with stirring for 5 hours at 135° C. The reaction mixture was cooled to 0° C., poured into 700 mL water, and the precipitate was filtered off to give the title compound (12.6 g, 38.2 mmol, 72% yield) as a grey solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.10 (s, 1H), 7.80 (s, 1H), 7.74 (s, 1H), 7.39-7.49 (m, 1H), 7.34 (t, 1H), 2.28 (s, 3H).

Workup

  1. temperaturethe mixture was heated
  2. stirringwith stirring for 5 hours at 135° C
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. filtrationthe precipitate was filtered off

Sources & evidence

ORD record
ord-aa00006f48ca4fb3ac3d3a51992f386b
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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