Methane → HCID 22716499, compound

HRID 1639669Notes

Reaction equation

HRID 1639669 reaction equation
[OH-].[K+].[Cl:3][C:4]1[CH:5]=[C:6]([C:9]#[N:10])[S:7][CH:8]=1.[O-:11]S([O-])(=O)=O.[Na+].[Na+].C>CCOC(C)=O.CCO.O>[Cl:3][C:4]1[CH:5]=[C:6]([C:9]([NH2:10])=[O:11])[S:7][CH:8]=1

Participants

8

Reactant 4

HCID 297MethaneHCID 14797Potassium HydroxideHCID 24436Sodium SulfateHCID 230580534-Chlorothiophene-2-carbonitrile

Product 1

HCID 22716499HCID 22716499, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
28 °C

Procedure

Equip a 12-L reaction flask with a cooling bath, air stirrer, and thermometer probe and charge with KOH (288.6 g, 5.143 moles) and water (6.04 L) to form a solution that exotherms to about 31° C. Allow the solution to cool to about 28° C., and charge the mixture with 4-chloro-2-thiophene carbonitrile (671.3 g, 4.675 moles) (a small amount of solids are undissolved). Add EtOH (675 mL), at which time a gradual exotherm occurs and continues over 1-1.5 h to about 38° C. Stir the reaction at ambient temperature overnight. Filter the reaction mixture under vacuum, wash with water, and dry to give crude product. Dissolve the solids in EtOAc (10.0 L), treat with Na2SO4 and activated charcoal for 1-2 h, then filter and wash with EtOAc. Concentrate the filtrate on a rotary evaporator at 45° C. until solids begin to precipitate out. Release the vacuum and increase the temperature to 60-65° C. to redissolve the solids. With stirring at 60° C., add heptane (3.5 L) slowly to precipitate solids. Stir for 15-20 min at 60° C., then cool the mixture to 30-40° C. and filter. Wash the solids with heptane (2×0.75 L), and dry to give the title compound as a white solid (235.4 g, 31%). Obtain a second crop (67.8 g, 9%) from the filtrate.

Workup

  1. customEquip
  2. customto form a solution that exotherms to about 31° C
  3. customthe reaction at ambient temperature overnight
  4. filtrationFilter the reaction mixture under vacuum
  5. washwash with water
  6. customdry
  7. customto give crude product
  8. filtrationfilter
  9. washwash with EtOAc
  10. concentrationConcentrate the filtrate
  11. customon a rotary evaporator at 45° C. until solids
  12. customto precipitate out
  13. temperatureincrease the temperature to 60-65° C.
  14. dissolutionto redissolve the solids
  15. stirringWith stirring at 60° C.
  16. additionadd heptane (3.5 L) slowly
  17. customto precipitate solids
  18. stirringStir for 15-20 min at 60° C.
  19. temperaturecool the mixture to 30-40° C.
  20. filtrationfilter
  21. washWash the solids with heptane (2×0.75 L)
  22. customdry

Sources & evidence

ORD record
ord-a0acf86ef82a489c95ce3b5e0a4fd2cf
Source dataset
uspto-grants-2012_02
Patent number
US08110580B2

Reaction notes

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