Cyclobutanone → 4-(4-((2-Cyanopropan-2-yl)amino)-2-fluorophenyl)butanenitrile

HRID 1504962Notes

Reaction equation

HRID 1504962 reaction equation
[Si]([C:5]#[N:6])(C)(C)C.[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][CH2:16][C:17]#[N:18])=[C:10]([F:19])[CH:9]=1.[C:20]1(=O)[CH2:23]C[CH2:21]1>O1CCOCC1.[Cl-].[Cl-].[Zn+2]>[C:5]([C:20]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][CH2:16][C:17]#[N:18])=[C:10]([F:19])[CH:9]=1)([CH3:23])[CH3:21])#[N:6]

Participants

6

Reactant 3

HCID 14496CyclobutanoneHCID 82115Trimethylsilyl cyanideHCID 576726094-(4-Amino-2-fluorophenyl)butanenitrile

Product 1

HCID 687342124-(4-((2-Cyanopropan-2-yl)amino)-2-fluorophenyl)butanenitrileYield 95.9%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 312751,4-DioxaneSolvent

Procedure

TMSCN (0.14 mL, 1.01 mmol) was added to a mixture of the compound 68 (60 mg, 0.34 mmol), cyclobutanone (0.15 mL, 2.04 mmol) and ZnCl2 (4 mg, 0.04 mmol) in dioxane (1 mL) with stirring. The reaction mixture was stirred at room temperature for 1 h, and concentrated in vacuo. The residue was diluted with water, and extracted with DCM. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated to dryness to give compound 70 (80 mg, 91%) as a light yellow oil. The crude product was used directly for the next step without purification.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 1 h
  2. concentrationconcentrated in vacuo
  3. additionThe residue was diluted with water
  4. extractionextracted with DCM
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-98eae07e7c6242a58aa77f98394f20dc
Source dataset
uspto-grants-2015_12
Patent number
US09216957B2

Reaction notes

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