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

HRID 869209Notes

Reaction equation

HRID 869209 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 NH4C(sat.) solution. The organic layer was washed with water (500 mL×2) and brine (500 mL), dried over Na2SO4, filtered, and concentrated to give a crude title compound (272 g, 90%), which was used in the next step without further purification, LRMS (M+H+) m/z 189.1.

Workup

  1. additionUpon completion of addition
  2. customquenched with NH4C(sat.) solution
  3. washThe organic layer was washed with water (500 mL×2) and brine (500 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-b333bac8656543d2b96269000da874d8
Source dataset
uspto-grants-2015_03
Patent number
US08969346B2

Reaction notes

Loading…