Dimethyl Sulfoxide → 1-[4-(Trifluoromethoxy)phenyl]cyclobutanecarbonitrile

HRID 1749146Notes

Reaction equation

HRID 1749146 reaction equation
[H-].[Na+].CS(C)=O.[F:7][C:8]([F:20])([F:19])[O:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][C:17]#[N:18])=[CH:12][CH:11]=1.Br[CH2:22][CH2:23][CH2:24]Br>C(OCC)C.C(O)(C)C.O>[F:7][C:8]([F:19])([F:20])[O:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2([C:17]#[N:18])[CH2:24][CH2:23][CH2:22]2)=[CH:14][CH:15]=1

Participants

8

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 80011,3-DibromopropaneHCID 24758Sodium hydrideHCID 1426764-(Trifluoromethoxy)phenylacetonitrile

Product 1

HCID 219020771-[4-(Trifluoromethoxy)phenyl]cyclobutanecarbonitrileYield 90%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 3776IsopropanolSolvent

Procedure

To sodium hydride (4.4 g, 110 mmol) was slowly added DMSO (100 mL) at 0° C. The mixture was warmed to room temperature and stirred for 10 minutes. A solution of 2-(4-(trifluoromethoxy)phenyl)acetonitrile (10.05 g, 50 mmol) and 1,3-dibromopropane (11.0 g, 55 mmol) in diethyl ether (50 ml) was added over 30 min at ≦30° C. Near the end of the addition, the mixture became very thick purple slurry that could not be stirred. An additional 50 mL of DMSO was added. After stirring for 75 min at room temperature, the reaction was complete according to LCMS. The reaction mixture was diluted with 25 mL of isopropanol and 15 mL of water, and extracted with ether. The organic layer was washed with water and brine, dried (Na2SO4), filtered, and concentrated to give the title compound. (10.85 g yield 90%).

Workup

  1. customat 0° C
  2. additionNear the end of the addition
  3. stirringbe stirred
  4. stirringAfter stirring for 75 min at room temperature
  5. extractionextracted with ether
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-696fff22958d414db819f16826c00bfa
Source dataset
uspto-grants-2015_10
Patent number
US09156788B2

Reaction notes

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