2,2,2-Trifluoroethanol → HCID 90204127, compound

HRID 1480188Notes

Reaction equation

HRID 1480188 reaction equation
Cl[C:2]1[C:7]([C:8]2([OH:12])[CH2:11][O:10][CH2:9]2)=[CH:6][N:5]=[C:4]([C:13]#[N:14])[CH:3]=1.[F:15][C:16]([F:20])([F:19])[CH2:17][OH:18].CC(C)([O-])C.[K+]>CN(C=O)C>[OH:12][C:8]1([C:7]2[C:2]([O:18][CH2:17][C:16]([F:20])([F:19])[F:15])=[CH:3][C:4]([C:13]#[N:14])=[N:5][CH:6]=2)[CH2:11][O:10][CH2:9]1

Participants

5

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 23665647Potassium tert-butoxideHCID 90204051HCID 90204051, compound

Product 1

HCID 90204127HCID 90204127, compoundYield 92.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-chloro-5-(3-hydroxyoxetan-3-yl)pyridine-2-carbonitrile (example 123b, 1 g, 4.75 mmol) in dry DMF (20 ml) under an argon atmosphere cooled down to 0° C. was added 2,2,2-trifluoroethanol (570 mg, 412 μl, 5.7 mmol) followed by addition of potassium tert-butoxide (639 mg, 5.7 mmol). The reaction was stirred at 0° C. for 10 minutes and then stirred at 80° C. for 2 hours. DMF was removed in vacuo and the residue was dissolved in ethylacetate. The organic phase was extracted with a 2M aqueous solution of sodium carbonate. The organic phase was collected and the aqueous phase back-extracted with ethylacetate. The combined organic phases were dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient to yield the title compound (1.2 gr, 92%); MS (ESI, m/z): 275.4 (M+H+).

Workup

  1. stirringstirred at 80° C. for 2 hours
  2. customDMF was removed in vacuo
  3. dissolutionthe residue was dissolved in ethylacetate
  4. extractionThe organic phase was extracted with a 2M aqueous solution of sodium carbonate
  5. customThe organic phase was collected
  6. extractionthe aqueous phase back-extracted with ethylacetate
  7. dry with materialThe combined organic phases were dried over sodium sulfate
  8. customevaporated down to dryness
  9. customThe crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient

Sources & evidence

ORD record
ord-1b50b799b3a44b71a2791bd469159b0a
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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