3-Methylenecyclobutanecarbonitrile → 1-(3-Fluoropyridin-2-yl)-3-methylenecyclobutane-1-carbonitrile

HRID 1853126Notes

Reaction equation

HRID 1853126 reaction equation
[CH2:1]=[C:2]1[CH2:5][CH:4]([C:6]#[N:7])[CH2:3]1.Cl[C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][N:10]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1(C)C=CC=CC=1>[F:15][C:14]1[C:9]([C:4]2([C:6]#[N:7])[CH2:5][C:2](=[CH2:1])[CH2:3]2)=[N:10][CH:11]=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 274743-MethylenecyclobutanecarbonitrileHCID 2724254Sodium bis(trimethylsilyl)amideHCID 27827912-Chloro-3-fluoropyridine

Product 1

HCID 674510301-(3-Fluoropyridin-2-yl)-3-methylenecyclobutane-1-carbonitrileYield 89,767.898%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 3-methylenecyclobutanecarbonitrile (150 g, 1.61 mol, 1 equiv) and 2-chloro-3-fluoropyridine (212 g, 1.61 mmol, 1 equiv) in toluene (1 L) was added NaHMDS (2 M in THF, 885 mL, 1.1 equiv) dropwise at 0-10° C. Upon completion of addition, the reaction mixture was warmed to rt, stirred overnight, and quenched with NH4Cl(sat) solution. The organic layer was washed with water (2×500 mL) and brine (500 mL), dried over Na2SO4, filtered, and concentrated to give the crude title compound (272 g, 90%) which was used in next step without further purification. LRMS (M+H+) m/z 189.1.

Workup

  1. additionUpon completion of addition
  2. customquenched with NH4Cl(sat) solution
  3. washThe organic layer was washed with water (2×500 mL) and brine (500 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-dd334a05c6a34bc98621465af6b8b3a4
Source dataset
uspto-grants-2015_02
Patent number
US08962632B2

Reaction notes

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