Trifluoroacetic acid → 4-Cyano-2-isobutylpyridine

HRID 660032Notes

Reaction equation

HRID 660032 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1)#[N:2].C(O)(=O)[CH2:10][CH:11]([CH3:13])[CH3:12].FC(F)(F)C(O)=O.[OH-].[Na+]>[N+]([O-])([O-])=O.[Ag+].ClC1C=CC=CC=1.O>[C:1]([C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH2:10][CH:11]([CH3:13])[CH3:12])[CH:4]=1)#[N:2]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 75064-CyanopyridineHCID 10430Isovaleric AcidHCID 14798Sodium Hydroxide

Product 1

HCID 146417864-Cyano-2-isobutylpyridineYield 54%

Reagents, catalysts & solvents 2

HCID 24470Silver NitrateCatalystHCID 19815812Chlorobenzene waterSolvent

Conditions

Temperature
0 °C

Procedure

p-cyanopyridine (8.00 g, 76.8 mmol) was added to a 1:1 mixture of chlorobenzene/water (1.5 L) in a 2 L round-bottom flask. Isovaleric acid (21.74 g, 212.8 mmol), (NH4)2S2O8 (34.40 g, 150.7 mmol), trifluoroacetic acid (8.78 g, 77.0 mmol) and AgNO3 (1.040 g, 6.1 mmol) were added and the heterogeneous mixture was vigorously stirred and refluxed for 2 h. The reaction was cooled down to 0° C. and 8 M NaOH was added slowly until pH 9-10. The mixture was filtered through Celite and extracted with EtOAc (×3). The combined organic extracts were dried with MgSO4 and the solvent removed in vacuo. The dark-brown oil was purified via flash chromatography (1:4 EtOAc/Hexane) to give a brown oil (6.538 g, 54%);

Workup

  1. temperaturerefluxed for 2 h
  2. filtrationThe mixture was filtered through Celite
  3. extractionextracted with EtOAc (×3)
  4. dry with materialThe combined organic extracts were dried with MgSO4
  5. customthe solvent removed in vacuo
  6. customThe dark-brown oil was purified via flash chromatography (1:4 EtOAc/Hexane)

Sources & evidence

ORD record
ord-1bc1b13d81f64304970f530af7fa27c3
Source dataset
uspto-grants-2011_12
Patent number
US08084471B2

Reaction notes

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