1,3-Dibromopropane → 1-(4-Bromo-2-fluorophenyl)cyclobutanecarbonitrile

HRID 1453142Notes

Reaction equation

HRID 1453142 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[C:4]([F:11])[CH:3]=1.Br[CH2:13][CH2:14][CH2:15]Br.[H-].[Na+].[Cl-].[NH4+]>CCOCC.CS(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:9]#[N:10])[CH2:15][CH2:14][CH2:13]2)=[C:4]([F:11])[CH:3]=1

Participants

7

Reactant 4

HCID 80011,3-DibromopropaneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 71723082-(4-Bromo-2-fluorophenyl)acetonitrile

Product 1

HCID 587626531-(4-Bromo-2-fluorophenyl)cyclobutanecarbonitrileYield 59.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolvent

Procedure

A solution of (4-bromo-2-fluoro-phenyl)-acetonitrile (4.0 g, 18.7 mmol) from step 1 and 1,3-dibromopropane (2.1 mL, 20.6 mmol) in Et2O (5 mL) was slowly added to a slurry of NaH (1.64 g, 41.1 mmol, 60% in mineral oil) in DMSO (19 mL) at room temperature, being careful to keep the temperature below 35 degrees Celsius. The reaction was stirred for 2.5 hours, and then poured into 150 mL of saturated ammonium chloride. To this mixture was added CH22Cl2, and the layers were separated. The aqueous layer was extracted with 2×50 mL of CH2Cl2, and the organic layers were combined. After drying the liquid over MgSO4, the solids were filtered away, and the organic was concentrated to an oil. It was further purified by flash chromatography (90 g SiO2, 1:99->1:20 (EtOAc/Hexanes) to give the desired product (2.81 g, 59%). 1H NMR (400 MHz, CDCl3) δ: 2.06-2.16 (m, H), 2.51-2.63 (m, H), 2.66-2.76 (qd, J=9347 Hz, 2H), 2.86-2.94 (m, 2H), 7.16-7.22 (t, J=8.21 Hz, H), 7.30-7.41 (m, 2H).

Workup

  1. customthe temperature below 35 degrees Celsius
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with 2×50 mL of CH2Cl2
  4. dry with materialAfter drying the liquid over MgSO4
  5. filtrationthe solids were filtered away
  6. concentrationthe organic was concentrated to an oil
  7. customIt was further purified by flash chromatography (90 g SiO2, 1:99->1:20 (EtOAc/Hexanes)

Sources & evidence

ORD record
ord-29be2792d80f49488ed2e9d34e221131
Source dataset
uspto-grants-2009_01
Patent number
US07473790B2

Reaction notes

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