2,2,2-Trifluoroethanol → HCID 22464526, compound

HRID 1935433Notes

Reaction equation

HRID 1935433 reaction equation
[F:1][C:2]([F:6])([F:5])[CH2:3][OH:4].[H-].[Na+].[C:9]([C:11]1[C:16](F)=[CH:15][CH:14]=[CH:13][N:12]=1)#[N:10]>C1COCC1>[C:9]([C:11]1[C:16]([O:4][CH2:3][C:2]([F:6])([F:5])[F:1])=[CH:15][CH:14]=[CH:13][N:12]=1)#[N:10]

Participants

5

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 70604082-Cyano-3-fluoropyridine

Product 1

HCID 22464526HCID 22464526, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A stirred solution of 680 mg (6.80 mmol) of 2,2,2-trifluoroethanol in 25 mL of THF was added 273 mg (6.83 mmol) of sodium hydride (60% dispersion). After 30 min at room temperature, 822 mg (6.73 mmol) of 2-cyano-3-fluoropyridine in 5 mL THF was added via syringe. The reaction was quenched after 1 h, by the addition of 15% K2CO3 aqueous solution. Concentration gave an oil that was partitioned between water and EtOAc. The layers were separated, the aqueous phase was backwashed with EtOAc (2×), and the combined organic layers were dried (MgSO4) and concentrated to an orange oil. The resultant crude residue was chromatographed on SiO2 using 25:75 EtOAc-hexanes to afford the title compound as a yellow oil: 1H NMR (CDCl3) δ8.43 (d,1H, 4.6 Hz), 7.55 (dd, 1H, 4.6, 8.7 Hz), 7.42 (d, 1H, 8.7 Hz), 4.55 (q, 2H, 7.8 Hz).

Workup

  1. customThe reaction was quenched after 1 h, by the addition of 15% K2CO3 aqueous solution
  2. concentrationConcentration
  3. customgave an oil that
  4. customwas partitioned between water and EtOAc
  5. customThe layers were separated
  6. dry with materialthe combined organic layers were dried (MgSO4)
  7. concentrationconcentrated to an orange oil
  8. customThe resultant crude residue was chromatographed on SiO2 using 25:75 EtOAc-hexanes

Sources & evidence

ORD record
ord-ced533eefe6843a190dd94a8336a23d3
Source dataset
uspto-grants-2002_05
Patent number
US06387911B1

Reaction notes

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