Cyanocyclobutane → 1-(5-Iodopyridin-2-YL)cyclobutanecarbonitrile

HRID 2038755Notes

Reaction equation

HRID 2038755 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][N:3]=1.[CH:9]1([C:13]#[N:14])[CH2:12][CH2:11][CH2:10]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1(C)C=CC=CC=1.[NH4+].[Cl-].C(Cl)Cl>[I:8][C:5]1[CH:6]=[CH:7][C:2]([C:9]2([C:13]#[N:14])[CH2:12][CH2:11][CH2:10]2)=[N:3][CH:4]=1

Participants

7

Reactant 3

HCID 78148CyanocyclobutaneHCID 2724254Sodium bis(trimethylsilyl)amideHCID 27831792-Fluoro-5-iodopyridine

Product 1

HCID 708006921-(5-Iodopyridin-2-YL)cyclobutanecarbonitrileYield 82.8%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

In a dry flask under argon, 2-fluoro-5-iodo-pyridine (3.85 g, 17.3 mmol) and cyclobutanecarbonitrile (1.40 g, 17 mmol) were dissolved in dry toluene (15 mL). The solution was cooled to 0° C. and sodium bis(trimethylsilyl)amide (1.0 M, 19 mL, 19 mmol) was added dropwise over 15 min. After 1 h, the solution was allowed to warm to room temperature and stirred for 26 h. The reaction was diluted with saturated aqueous NH4Cl (10 mL) and CH2Cl2 (10 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (2×10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to yield 4.0 g of 1-(5-iodo-pyridin-2-yl)-cyclobutane carbonitrile as a viscous, light brown oil, m/z 285.4 [M+H]+.

Workup

  1. temperatureto warm to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with CH2Cl2 (2×10 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-608ef93d707c4a63951f80d883ae88e3
Source dataset
uspto-grants-2013_11
Patent number
US08575360B2

Reaction notes

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