Isopropanol → 1-(4-Methoxyphenyl)cyclobutane-1-carbonitrile

HRID 1160335Notes

Reaction equation

HRID 1160335 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]#[N:11])=[CH:5][CH:4]=1.Br[CH2:13][CH2:14][CH2:15]Br.[H-].[Na+].CC(O)C>CCOCC.CS(C)=O.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([C:10]#[N:11])[CH2:15][CH2:14][CH2:13]2)=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 3776IsopropanolHCID 80011,3-DibromopropaneHCID 24758Sodium hydrideHCID 66031Benzeneacetonitrile, 4-methoxy-

Product 1

HCID 219020981-(4-Methoxyphenyl)cyclobutane-1-carbonitrileYield 62.5%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

A solution of 3.27 g (22.2 mmol) of (4-methoxyphenyl)acetonitrile and 4.93 g (24.4 mmol) of 1,3-dibromopropane in 15 mL of ether was added dropwise into 1.17 g (48.8 mmol) of NaH in 60 mL of DMSO. The temperature was held between 250 and 35° by water bath cooling. The mixture was stirred at room temperature for 18 hours. The mixture was cooled in ice water and 3 mL of 2-propanol was added dropwise, followed by the addition of 50 mL of water. The mixture was extracted with hexane (3×100 mL), and the combined extracts were washed with water (3×75 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated to yield 2.6 g (62%) product as colorless oil. 1H NMR (CDCl3) δ 2.01-2.14 (m, 1H), 2.35-2.50 (m, 1H), 2.55-2.66 (m, 2H), 2.77-2.87 (m, 2H), 3.83 (s, 3H), 6.94 (d, J=9.0 Hz, 2H), 7.36 (d, J=9.0 Hz, 2H). 13C NMR (CDCl3) δ 17.3, 35.1, 39.9, 55.6, 114.5, 124.9, 127.0, 132.1, 159.4.

Workup

  1. customThe temperature was held between 250 and 35° by water bath
  2. temperaturecooling
  3. extractionThe mixture was extracted with hexane (3×100 mL)
  4. washthe combined extracts were washed with water (3×75 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-39d1bdcfc7564c4ca9a1bceffccdd5a5
Source dataset
uspto-grants-2010_10
Patent number
US07816375B2

Reaction notes

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