(Trifluoromethyl)trimethylsilane → 2-Pyridinecarbonitrile, 5-(2,2,2-trifluoro-1-hydroxyethyl)-

HRID 1025282Notes

Reaction equation

HRID 1025282 reaction equation
[CH:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]#[N:10])=[N:7][CH:8]=1)=[O:2].C[Si](C)(C)[C:13]([F:16])([F:15])[F:14]>C1COCC1>[F:14][C:13]([F:16])([F:15])[CH:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]#[N:10])=[N:7][CH:8]=1)[OH:2]

Participants

4

Reactant 2

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 109862635-Formylpyridine-2-carbonitrile

Product 1

HCID 670859302-Pyridinecarbonitrile, 5-(2,2,2-trifluoro-1-hydroxyethyl)-Yield 39.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a −78° C. solution of 5-formylpicolinonitrile (1.0 g, 7.58 mmol) and tetrabutylammonium triphenyldifluorosilicate (4.9 g, 9.10 mmol) in 60 mL of THF was added a solution of trimethyl(trifluoromethyl)silane (1.62 g, 114 mmol). The mixture was stirred for 20 min at −78° C. Then the cooling bath was changed to an ice bath. After stirring for another 30 min, the reaction was quenched with sat. NH4Cl(aq.). The mixture was extracted with EtOAc (3×). The organic layer was washed with sat. NaHCO3 (aq.), brine, then dried (MgSO4) and concentrated. The product 5-(2,2,2-trifluoro-1-hydroxyethyl)picolinonitrile (600 mg) was obtained by silica gel chromatography (elution with 0-40% EtOAc/Hex).

Workup

  1. customThen the cooling bath was changed to an ice bath
  2. stirringAfter stirring for another 30 min
  3. customthe reaction was quenched with sat. NH4Cl(aq.)
  4. extractionThe mixture was extracted with EtOAc (3×)
  5. washThe organic layer was washed with sat. NaHCO3 (aq.), brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-be0e4e41a26c48949af64e19a637cd3f
Source dataset
uspto-grants-2014_05
Patent number
US08729071B2

Reaction notes

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