Potassium Carbonate → HCID 71116075, compound

HRID 1423825Notes

Reaction equation

HRID 1423825 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH3:7][C@:8]1([CH2:30][NH2:31])[CH2:29][CH2:28][CH2:27][C:10]2([O:14][C@H:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C@@H:12]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[O:11]2)[CH2:9]1.F[C:33]1[CH:34]=[C:35]([CH:38]=[CH:39][C:40]=1[N+:41]([O-:43])=[O:42])[C:36]#[N:37]>C(#N)C>[CH3:7][C@:8]1([CH2:30][NH:31][C:39]2[CH:38]=[C:35]([CH:34]=[CH:33][C:40]=2[N+:41]([O-:43])=[O:42])[C:36]#[N:37])[CH2:29][CH2:28][CH2:27][C:10]2([O:11][C@H:12]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C@@H:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[O:14]2)[CH2:9]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27833993-Fluoro-4-nitrobenzonitrileHCID 71116094HCID 71116094, compound

Product 1

HCID 71116075HCID 71116075, compoundYield 70.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

A solution of acetonitrile (2049 mL) in a 3 L flask was heated to 40° C. Next, potassium carbonate (198 g, 1434 mmol), 1-[(2R,3R,7S)-7-methyl-2,3-diphenyl-1,4-dioxaspiro[4.5]dec-7-yl]methanamine (242 g, 717 mmol) and 3-fluoro-4-nitrobenzonitrile (119 g, 717 mmol) were added slowly. The mixture was allowed to stir at 40° C. for 2 h, and then cooled to RT. Stirring was continued at RT overnight. The next day, the slurry was filtered and the solids were washed with acetonitrile (500 mL). The filtrate was concentrated to afford the crude product (while keeping the temperature ˜60° C. during concentration). To the thick dark residue was added MeOH. The solution was heated to 60° C. on the rotovap and concentrated to a minimal volume. To the residue was added ˜500 mL of MeOH slowly with heating to avoid rapid crystallization, and the solution was heated to reflux. Once at reflux, an additional 250 mL MeOH was slowly added. The resulting slurry was allowed to stir at reflux for about 60 min, then heating was stopped and the slurry was allowed to cool to RT and stirring was continued for 3 days. The slurry was cooled to ˜10° C. with an ice/water bath. Stirring was continued for ˜2 h, and then the slurry was filtered and washed with cold MeOH (100 mL). The solids were dried under reduced pressure to give the desired product as a bright orange solid (245 g, 70.7% yield).

Workup

  1. temperaturecooled to RT
  2. stirringStirring
  3. waitwas continued at RT overnight
  4. filtrationThe next day, the slurry was filtered
  5. washthe solids were washed with acetonitrile (500 mL)
  6. concentrationThe filtrate was concentrated
  7. customto afford the crude product (
  8. customthe temperature ˜60° C.
  9. concentrationduring concentration)
  10. additionTo the thick dark residue was added MeOH
  11. temperatureThe solution was heated to 60° C. on the rotovap
  12. concentrationconcentrated to a minimal volume
  13. additionTo the residue was added ˜500 mL of MeOH slowly
  14. temperaturewith heating
  15. customcrystallization
  16. temperaturethe solution was heated to reflux
  17. temperatureOnce at reflux
  18. additionan additional 250 mL MeOH was slowly added
  19. stirringto stir
  20. temperatureat reflux for about 60 min
  21. temperatureheating
  22. temperatureto cool to RT
  23. stirringstirring
  24. waitwas continued for 3 days
  25. temperatureThe slurry was cooled to ˜10° C. with an ice/water bath
  26. stirringStirring
  27. waitwas continued for ˜2 h
  28. filtrationthe slurry was filtered
  29. washwashed with cold MeOH (100 mL)
  30. customThe solids were dried under reduced pressure

Sources & evidence

ORD record
ord-339827df1c7a4688b9db97cff0012043
Source dataset
uspto-grants-2015_01
Patent number
US08927585B2

Reaction notes

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