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

HRID 858612Notes

Reaction equation

HRID 858612 reaction equation
[H-].[Na+].Br[CH2:4][CH2:5][CH2:6]Br.[Br:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]#[N:17])=[C:11]([F:18])[CH:10]=1.[Cl-].[NH4+]>CS(C)=O.C(OCC)C.C(Cl)Cl>[Br:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2([C:16]#[N:17])[CH2:6][CH2:5][CH2:4]2)=[C:11]([F:18])[CH:10]=1

Participants

8

Reactant 4

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

Product 1

HCID 587626531-(4-Bromo-2-fluorophenyl)cyclobutanecarbonitrile

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a slurry of NaH (1.64 g, 60% suspension in mineral oil, 41.1 mmol) in DMSO (19 mL) stirred at room temperature, was added a solution of 1,3-dibromopropane (2.1 mL, 20.6 mmol) and (4-Bromo-2-fluoro-phenyl)-acetonitrile (4.0 g, 18.7 mmol) in diethyl ether (10 mL) slowly keeping the temprature of the reaction between 25 degrees Celsius and 35 degrees Celsius. Stir for two hours after the addition is complete, and pour into saturated ammonium chloride (150 mL). Add 100 ml of CH2Cl2 and separate the layers. Extract the aqueous phase with 2×50 mL CH2Cl2 and combine the organics. After drying the organic liquid over MgSO4, the solids were removed by filtration, and the liquid was concentrated to an oil. The oil was purified by flash chromatography to yield the desired product. Yield: 1.43 g, 30%.

Workup

  1. customthe temprature of the reaction between 25 degrees Celsius and 35 degrees Celsius
  2. additionafter the addition
  3. customseparate the layers
  4. extractionExtract the aqueous phase with 2×50 mL CH2Cl2
  5. dry with materialAfter drying the organic liquid over MgSO4
  6. customthe solids were removed by filtration
  7. concentrationthe liquid was concentrated to an oil
  8. customThe oil was purified by flash chromatography

Sources & evidence

ORD record
ord-99e6ff83b7a44d9982a74299997234c1
Source dataset
uspto-grants-2006_12
Patent number
US07148226B2

Reaction notes

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