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

HRID 1504961Notes

Reaction equation

HRID 1504961 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.[CH3:20][C:21]([CH3:23])=O>[Cl-].[Cl-].[Zn+2]>[C:5]([C:21]([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])[CH3:20])#[N:6]

Participants

5

Reactant 3

HCID 180AcetoneHCID 82115Trimethylsilyl cyanideHCID 576726094-(4-Amino-2-fluorophenyl)butanenitrile

Product 1

HCID 687342124-(4-((2-Cyanopropan-2-yl)amino)-2-fluorophenyl)butanenitrileYield 96.4%

Reagents, catalysts & solvents 1

HCID 3007855ZincchlorideCatalyst

Procedure

TMSCN (0.37 mL, 2.78 mmol) was added to a mixture of compound 68 (165 mg, 0.93 mmol), acetone (0.41 mL, 5.58 mmol) and ZnCl2 (12 mg, 0.09 mmol) 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 69 (220 mg, 96%) as a light yellow oil. The crude product was used directly for the next step without purification. 1H NMR (400 MHz, CDCl3) δ7.02-7.10 (m, 1H), 6.58-6.65 (m, 2H), 2.72 (t, 2H, J=7.3 Hz), 2.34 (t, 2H, J=7.1 Hz), 1.90-2.00 (m, 2H), 1.71 (s, 6H).

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-2f8c921acdd64f60845c597f82020a8e
Source dataset
uspto-grants-2015_12
Patent number
US09216957B2

Reaction notes

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