Cyanocyclobutane → 1344145-52-3

HRID 1853118Notes

Reaction equation

HRID 1853118 reaction equation
Cl[C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH:9]1([C:13]#[N:14])[CH2:12][CH2:11][CH2:10]1.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>C1(C)C=CC=CC=1>[F:8][C:7]1[C:2]([C:9]2([C:13]#[N:14])[CH2:12][CH2:11][CH2:10]2)=[N:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 78148CyanocyclobutaneHCID 2724254Sodium bis(trimethylsilyl)amideHCID 27827912-Chloro-3-fluoropyridine

Product 1

HCID 674528781344145-52-3Yield 83%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a 0° C. solution of 2-chloro-3-fluoropyridine (80.0 g, 611 mmol, 1.0 equiv) and cyclobutane carbonitrile (49.5 g, 611 mmol, 1.0 equiv) in toluene (500 mL) was added sodium hexamethyldisilazide (2.0 M in THF, 306 mL, 612 mmol, 1.0 equiv) in a dropwise manner. The resulting mixture was allowed to slowly warm to room temperature and stirred overnight. The reaction was then quenched with water (500 mL), and the organic layer was separated from the aqueous layer. The aqueous layer was extracted with EtOAc (2×300 mL), and the combined organic phases were washed with saturated brine solution (2×400 mL), dried over Na2SO4, concentrated to give a crude yellow oil, and chromatographed with silica gel (2-10% EtOAc/hex) to give 1-(3-fluoropyridin-2-yl)cyclobutanecarbonitrile (88 g, 83%) as a pale yellow oil.

Workup

  1. customThe reaction was then quenched with water (500 mL)
  2. customthe organic layer was separated from the aqueous layer
  3. extractionThe aqueous layer was extracted with EtOAc (2×300 mL)
  4. washthe combined organic phases were washed with saturated brine solution (2×400 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto give a crude yellow oil
  8. customchromatographed with silica gel (2-10% EtOAc/hex)

Sources & evidence

ORD record
ord-4c2c77ef07894d9aa5c9d67b2cb633cf
Source dataset
uspto-grants-2015_02
Patent number
US08962632B2

Reaction notes

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