Sulfuric Acid → HCID 90203676, compound

HRID 1480166Notes

Reaction equation

HRID 1480166 reaction equation
[F:1][C:2]([F:17])([F:16])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1[C:11]1(O)[CH2:14][CH2:13][CH2:12]1.S(=O)(=O)(O)O.[H][H]>C(O)C.[Pd]>[CH:11]1([C:6]2[CH:7]=[N:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][C:2]([F:17])([F:1])[F:16])[CH2:12][CH2:13][CH2:14]1

Participants

6

Reactant 3

HCID 1118Sulfuric AcidHCID 90204115HCID 90204115, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 90203676HCID 90203676, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 1-[4-(2,2,2-Trifluoro-ethoxy)-pyridin-3-yl]-cyclobutanol (Example 108b, 3.88 g, 15.7 mmol) in ethanol (50 ml) under argon atmosphere was added sulfuric acid 97% (4.62 g, 2.51 ml, 47.1 mmol) and palladium(0) on charcoal 10% (384 mg, 3.61 mmol). The reaction vessel was pressurized with hydrogen to 2.5 bar and stirred at 50° C. for 18 hours. The reaction mixture was cooled down to room temperature, filtered through a pad of Celite and the filter cake was washed twice with ethanol. The filtrate was evaporated down to dryness, the residue was dissolved in ethylacetate and extracted with an 2.0M aqueous solution of sodium carbonate. The organic phase was collected and the aqueous phase was back-extracted with ethylacetate. The organic phases were combined, dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a dichloromethane/methanol gradient to yield the title compound (3.05 g, 84%) as yellow oil. MS (ESI, m/z): 232.6 (M+H+).

Workup

  1. temperatureThe reaction mixture was cooled down to room temperature
  2. filtrationfiltered through a pad of Celite
  3. washthe filter cake was washed twice with ethanol
  4. customThe filtrate was evaporated down to dryness
  5. dissolutionthe residue was dissolved in ethylacetate
  6. extractionextracted with an 2.0M aqueous solution of sodium carbonate
  7. customThe organic phase was collected
  8. extractionthe aqueous phase was back-extracted with ethylacetate
  9. dry with materialdried over sodium sulfate
  10. customevaporated down to dryness
  11. customThe crude material was purified by flash chromatography on silica eluting with a dichloromethane/methanol gradient

Sources & evidence

ORD record
ord-d2d820c2a07c4732ae78e9066d360d0e
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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