Ethanol → 6-(3,3,3-Trifluoropropyl)pyridine-3-carboxylic acid

HRID 341525Notes

Reaction equation

HRID 341525 reaction equation
[F:1][C:2]([F:14])([F:13])[CH2:3][CH2:4][C:5]1[N:10]=[CH:9]C(C#N)=[CH:7][CH:6]=1.[OH-:15].[K+].[CH3:17][CH2:18][OH:19]>>[F:1][C:2]([F:14])([F:13])[CH2:3][CH2:4][C:5]1[N:10]=[CH:9][C:17]([C:18]([OH:15])=[O:19])=[CH:7][CH:6]=1

Participants

4

Reactant 3

HCID 702EthanolHCID 14797Potassium Hydroxide2×HCID 668031346-(3,3,3-Trifluoropropyl)pyridine-3-carbonitrile2×

Product 1

HCID 668032656-(3,3,3-Trifluoropropyl)pyridine-3-carboxylic acidYield 89%

Procedure

To a solution of 6-(3,3,3-trifluoropropyl)pyridine-3-carbonitrile (Intermediate 208, 189 mg, 0.945 mmol) in EtOH (20 mL) was added potassium hydroxide (265 mg, 4.72 mmol). The solution was heated at 100 C for 6 h and then additional potassium hydroxide (53 mg, 0.94 mmol) added. After stirring for a further 3 h at 105 C, the reaction mixture was cooled to room temperature, evaporated to dryness and re-dissolved in water (20 mL). The solution was acidified to pH 3 with a 1M aq. HCl solution and extracted with EtOAc (3×25 mL). Combined organics were dried over magnesium sulfate and evaporated to dryness to afford the title compound as a light brown solid (183 mg, 89%). Method C HPLC-MS: MH+ requires m/z=220. Found: m/z=220, Rt=1.12 min (91%).

Workup

  1. temperatureThe solution was heated at 100 C for 6 h
  2. customevaporated to dryness
  3. dissolutionre-dissolved in water (20 mL)
  4. extractionextracted with EtOAc (3×25 mL)
  5. dry with materialCombined organics were dried over magnesium sulfate
  6. customevaporated to dryness

Sources & evidence

ORD record
ord-eb1b3a6ec2324e37b5f1d0d9800ec349
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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