Ammonium Acetate → HCID 57431079, compound

HRID 1895575Notes

Reaction equation

HRID 1895575 reaction equation
C(O[CH:4]=[CH:5][C:6](=O)[C:7]([F:10])([F:9])[F:8])C.[CH3:12][S:13][CH2:14][CH:15]=[CH:16][N:17]1CCCC1.C([O-])(=O)C.[NH4+]>C(#N)C>[CH3:12][S:13][CH2:14][C:15]1[CH:4]=[CH:5][C:6]([C:7]([F:8])([F:9])[F:10])=[N:17][CH:16]=1

Participants

5

Reactant 3

HCID 517165Ammonium AcetateHCID 27803954-Ethoxy-1,1,1-trifluoro-3-buten-2-oneHCID 76538844HCID 76538844, compound

Product 1

HCID 57431079HCID 57431079, compoundYield 85.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a dry 1 L round bottom flask equipped with a magnetic stir bar, liquid addition funnel, thermometer, and nitrogen inlet were added 4-ethoxy-1,1,1-trifluorobut-3-en-2-one (M) (67.4 g, 401 mmol) and 133 mL of anhydrous acetonitrile, and the resulting solution was cooled to 0° C. in an ice bath. To this solution was added 1-[3-(methylthio)prop-1-enyl]pyrrolidine (L) (63.0 g, 401 mmol, dissolved in 50 mL of anhydrous acetonitrile) dropwise via the addition funnel at a rate which maintained the reaction temperature at 0-7° C. The ice bath was removed and the resulting burgundy solution was warmed to room temperature and stirred for 2 hours. Ammonium acetate (46.3 g, 601 mmol) was added and the reaction was heated to reflux and stirred for 5 hours, and then stirred at room temperature for 16 hours. The acetonitrile was evaporated on the rotary evaporator and the residue was dissolved in 1 L of Et2O, washed with water (3×200 mL), dried (Na2SO4), filtered, and the Et2O removed on the rotary evaporator to give 83.4 g of the crude pyridine as a dark-red oil. Flash chromatography (SiO2, 25→70% EtOAc/Hexanes) afforded 70.8 g (85%) of 5-[(methylthio)methyl]-2-(trifluoromethyl)pyridine (N) as an orange oil. 1H NMR (CDCl3) δ 8.64 (d, 1H), 7.86 (dd, 1H), 7.66 (d, 1H), 3.73 (s, 2H), 2.02 (s, 3H). GC-MS (EI) m/z 207 (M+).

Workup

  1. customTo a dry 1 L round bottom flask equipped with a magnetic stir bar, liquid addition funnel
  2. temperaturemaintained the reaction temperature at 0-7° C
  3. customThe ice bath was removed
  4. temperaturethe resulting burgundy solution was warmed to room temperature
  5. temperaturethe reaction was heated
  6. temperatureto reflux
  7. stirringstirred for 5 hours
  8. stirringstirred at room temperature for 16 hours
  9. customThe acetonitrile was evaporated on the rotary evaporator
  10. dissolutionthe residue was dissolved in 1 L of Et2O
  11. washwashed with water (3×200 mL)
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. customthe Et2O removed on the rotary evaporator
  15. customto give 83.4 g of the crude pyridine as a dark-red oil

Sources & evidence

ORD record
ord-2f72b5f962f045a499f1b86e05156ca5
Source dataset
uspto-grants-2013_08
Patent number
US08513462B2

Reaction notes

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