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

HRID 1160337Notes

Reaction equation

HRID 1160337 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.Br[CH2:12][CH2:13][CH2:14]Br.[H-].[Na+].CC(O)C>CCOCC.CS(C)=O.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:9]#[N:10])[CH2:14][CH2:13][CH2:12]2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 3776IsopropanolHCID 80011,3-DibromopropaneHCID 24758Sodium hydrideHCID 68016Benzeneacetonitrile, 4-fluoro-

Product 1

HCID 219020361-(4-Fluorophenyl)cyclobutane-1-carbonitrileYield 61%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

A solution of 3.00 g (22.2 mmol) of 4-fluorophenylacetonitrile 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 2.35 g (61%) product as colorless oil. 1H NMR (CDCl3) δ 2.03-2.16 (m, 1H), 2.38-2.53 (m, 1H), 2.58-2.67 (m, 21), 2.80-2.90 (m, 2H), 7.11 (dd, J=9.0, 8.4 Hz, 2H), 7.41 (dd, J=9.1, 5.1 Hz, 2H). 13C NMR (CDCl3) 17.3, 35.0, 39.9, 116.1 (d, J=21.5 Hz), 124.5, 127.7, 135.9, 162.5 (d, J=230 Hz).

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-64e0bec29a374e15aaea9b2588a74051
Source dataset
uspto-grants-2010_10
Patent number
US07816375B2

Reaction notes

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