Dimethyl Sulfoxide → 1-[3-(Trifluoromethyl)phenyl]cyclobutane-1-carbonitrile

HRID 1620995Notes

Reaction equation

HRID 1620995 reaction equation
[H-].[Na+].CS(C)=O.[F:7][C:8]([F:19])([F:18])[C:9]1[CH:10]=[C:11]([CH2:15][C:16]#[N:17])[CH:12]=[CH:13][CH:14]=1.Br[CH2:21][CH2:22][CH2:23]Br>CC(OC)(C)C>[F:7][C:8]([F:18])([F:19])[C:9]1[CH:10]=[C:11]([C:15]2([C:16]#[N:17])[CH2:23][CH2:22][CH2:21]2)[CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 80011,3-DibromopropaneHCID 24758Sodium hydrideHCID 75360m-Trifluoromethylphenylacetonitrile

Product 1

HCID 224067101-[3-(Trifluoromethyl)phenyl]cyclobutane-1-carbonitrileYield 67.9%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

The mixture of sodium hydride (1.312 g, 54.7 mmol) and DMSO was stirred for about 10 minutes at room temperature. Then a solution of 2-(3-(trifluoromethyl)phenyl)acetonitrile (5 g, 24.86 mmol) and 1,3-dibromopropane (5.02 g, 24.86 mmol) in MTBE (80 mL) was added dropwise via dropping funnel. After addition, the mixture was stirred for about 12 hours, and quenched with 60 mL of water. The aqueous phase was extracted with MTBE (3×30 mL). The combined organic layers were washed with water (3×30 mL) and brine (3×30 mL), dried over sodium sulfate, filtered, and concentrated. The residue was chromatographed on silica gel column (20:1 Hexanes/ethyl acetate) to obtain the title compound as a transparent liquid (3.8 g, 63.4%). LC-MS: m/z (M+H) 226.

Workup

  1. additionAfter addition
  2. stirringthe mixture was stirred for about 12 hours
  3. customquenched with 60 mL of water
  4. extractionThe aqueous phase was extracted with MTBE (3×30 mL)
  5. washThe combined organic layers were washed with water (3×30 mL) and brine (3×30 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed on silica gel column (20:1 Hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-c243800d208045b78c1bbf94c514d7ca
Source dataset
uspto-grants-2014_07
Patent number
US08772500B2

Reaction notes

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