Potassium Carbonate → HCID 68518393, compound

HRID 883575Notes

Reaction equation

HRID 883575 reaction equation
C([O-])([O-])=O.[K+].[K+].[ClH:7].Cl.Br[C:10]1[CH:11]=[C:12]([CH2:19][N:20]2[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]2)[CH:13]=[CH:14][C:15]=1[N+:16]([O-:18])=[O:17].Cl.[NH2:28][C:29]1[S:33][C:32]([C:34]([O:36][CH3:37])=[O:35])=[C:31]([O:38][C@@H:39]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=2[C:47]([F:50])([F:49])[F:48])[CH3:40])[CH:30]=1>O>[ClH:7].[ClH:7].[CH3:26][N:23]1[CH2:24][CH2:25][N:20]([CH2:19][C:12]2[CH:13]=[CH:14][C:15]([N+:16]([O-:18])=[O:17])=[C:10]([NH:28][C:29]3[S:33][C:32]([C:34]([O:36][CH3:37])=[O:35])=[C:31]([O:38][C@@H:39]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=4[C:47]([F:50])([F:48])[F:49])[CH3:40])[CH:30]=3)[CH:11]=2)[CH2:21][CH2:22]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 68512661HCID 68512661, compoundHCID 68518643HCID 68518643, compound

Product 1

HCID 68518393HCID 68518393, compoundYield 173%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
27.5 °C

Procedure

K2CO3 (100 g) was dissolved in water (225 mL) and the resulting solution was cooled to 25-30° C. 1-[(3-bromo-4-nitrophenyl)methyl]-4-methylpiperazine dihydrochloride (50.0 g), methyl 5-amino-3-({(1R)-1-[2-(trifluoromethyl)phenyl]ethyl}oxy)-2-thiophenecarboxylate hydrochloride (53.7 g) and 2-methyl THF (250 mL) were added and the mixture was stirred until complete dissolution had taken place. The layers were separated, retaining the organic phase. 2-Methyl tetrahydrofuran (40 mL) was added and the mixture was distilled under reduced pressure to a volume of 350-400 mL. Xantphos (2.32 g, 3 mol %) was added, followed by cesium carbonate (48.0 g) and tris(benzylideneacetone)dipalladium(0) (1.84 g, 1.5 mol %). The reaction mixture was heated to 70-75° C. until judged complete by HPLC and then cooled to 20° C. Water (250 mL) was added and the mixture stirred to dissolve the inorganics. The mixture was filtered through celite, then the phases allowed to separate. The aqueous phase was discarded. The celite was washed with MeOH (200 mL). The MeOH wash was added to the previous organic phase. The mixture was slowly added to 5 M aqueous HCl over approximately 40 minutes. The resulting crystalline slurry was stirred overnight at room temperature, then filtered, washing with MeOH (100 mL, cooled to 0° C.) and dried under reduced pressure to give the title compound (72.8 g, 87% th) as orange to red crystalline sold.

Workup

  1. customThe layers were separated
  2. addition2-Methyl tetrahydrofuran (40 mL) was added
  3. distillationthe mixture was distilled under reduced pressure to a volume of 350-400 mL
  4. additionXantphos (2.32 g, 3 mol %) was added
  5. temperatureThe reaction mixture was heated to 70-75° C.
  6. temperaturecooled to 20° C
  7. additionWater (250 mL) was added
  8. stirringthe mixture stirred
  9. dissolutionto dissolve the inorganics
  10. filtrationThe mixture was filtered through celite
  11. customto separate
  12. washThe celite was washed with MeOH (200 mL)
  13. washThe MeOH wash
  14. additionwas added to the previous organic phase
  15. additionThe mixture was slowly added to 5 M aqueous HCl over approximately 40 minutes
  16. stirringThe resulting crystalline slurry was stirred overnight at room temperature
  17. filtrationfiltered
  18. washwashing with MeOH (100 mL, cooled to 0° C.)
  19. customdried under reduced pressure

Sources & evidence

ORD record
ord-570937ec7bc54b6eac6cf497432577e7
Source dataset
uspto-grants-2012_08
Patent number
US08236954B2

Reaction notes

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