Tetrahydrofuran → 1-(Pyridin-2-yl)cyclobutane-1-carbonitrile

HRID 1040486Notes

Reaction equation

HRID 1040486 reaction equation
F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[CH:8]1([C:12]#[N:13])[CH2:11][CH2:10][CH2:9]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C1COCC1>C1(C)C=CC=CC=1.[NH4+].[Cl-].C(Cl)Cl>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:8]1([C:12]#[N:13])[CH2:11][CH2:10][CH2:9]1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 97462-FluoropyridineHCID 78148CyanocyclobutaneHCID 2724254Sodium bis(trimethylsilyl)amide

Product 1

HCID 529881351-(Pyridin-2-yl)cyclobutane-1-carbonitrileYield 80%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

In a dry flask under Ar, 2-fluoropyridine (3.18 ml, 37 mmol) and cyclobutanecarbonitrile (3.0 g, 37 mmol) were dissolved in toluene (55 mL). The solution was cooled to 0° C. A 1M solution of sodium bis(trimethylsilyl)amide in THF (40.7 mL, 40.7 mmol) was added slowly over 5 min. After 1 h, the solution was warmed to room temperature. After another 19 h, the reaction was diluted with NH4Cl (aq) and DCM. The layers were separated. The aqueous layer was extracted with DCM. The combined organic layers were dried over MgSO4, filtered and concentrated to yield 4.68 g (80%) of 1-pyridin-2-yl-cyclobutanecarbonitrile as a pale yellow oil, m/z=159.7 [M+1]+.

Workup

  1. temperaturethe solution was warmed to room temperature
  2. waitAfter another 19 h
  3. customThe layers were separated
  4. extractionThe aqueous layer was extracted with DCM
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-60a27b980b3d47e6b059705f4e3d2aee
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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