Hydrogen Bromide → Methyl 5-(piperazin-1-yl)benzofuran-2-carboxylate

HRID 628795Notes

Reaction equation

HRID 628795 reaction equation
C1(S([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[CH:17]=[CH:18][C:19]4[O:23][C:22]([C:24]([O:26][CH3:27])=[O:25])=[CH:21][C:20]=4[CH:28]=3)[CH2:12][CH2:11]2)(=O)=O)C=CC=CC=1.Br.Cl>C(O)(=O)C.OC1C=CC(C(O)=O)=CC=1>[N:13]1([C:16]2[CH:17]=[CH:18][C:19]3[O:23][C:22]([C:24]([O:26][CH3:27])=[O:25])=[CH:21][C:20]=3[CH:28]=2)[CH2:12][CH2:11][NH:10][CH2:15][CH2:14]1

Participants

6

Reactant 3

HCID 260Hydrogen BromideHCID 313Hydrochloric AcidHCID 90022245Methyl 5[4-(benzenesulfonyl)-1-piperazinyl]benzofuran-2-carboxylate

Product 1

HCID 77231352Methyl 5-(piperazin-1-yl)benzofuran-2-carboxylateYield 82.5%

Reagents, catalysts & solvents 2

HCID 1354-Hydroxybenzoic AcidSolventHCID 176Acetic AcidSolvent

Conditions

Temperature
27.5 °C

Procedure

Methyl 5[4-(benzenesulfonyl)-1-piperazinyl]benzofuran-2-carboxylate (30 g) was added to a solution of hydrobromic acid in acetic acid (180 ml) and 4-hydroxybenzoic acid (24 g). The resulting mixture was stirred for 5 minutes at 25-30° C., followed by heating the mixture to 80-85° C. and maintaining for 6 hours at the same temperature. The reaction mass was poured into methanolic HCl (1000 ml), followed by heating to reflux and then stirring for 6 hours under reflux. The resulting mass was cooled to 0-5° C. and then stirred for 1 hour at the same temperature. The separated solid was filtered and washed with chilled methanol (100 ml). The wet solid was added to methanolic HCl (500 ml) and then heated to reflux for 4 hours. The resulting mass was cooled to 0-5° C. and then stirred for 1 hour at the same temperature. The separated solid was filtered, washed with chilled methanol (100 ml) and then dried at 60-65° C. The resulting solid was added to toluene (500 ml) at 25-30° C., followed by purging ammonia gas slowly for 7 hours. After completion of the ammonia gas purging, the reaction mass was stirred for 15 minutes at 25-30° C. The resulting mass was filtered and the filtrate was distilled to produce 16 g of methyl 5-(1-piperazinyl)benzofuran-2-carboxylate (Purity by HPLC: 99.5%; Yield: 82.5%).

Workup

  1. temperatureby heating the mixture to 80-85° C.
  2. temperaturemaintaining for 6 hours at the same temperature
  3. temperatureby heating
  4. temperatureto reflux
  5. stirringstirring for 6 hours
  6. temperatureunder reflux
  7. temperatureThe resulting mass was cooled to 0-5° C.
  8. stirringstirred for 1 hour at the same temperature
  9. filtrationThe separated solid was filtered
  10. washwashed with chilled methanol (100 ml)
  11. additionThe wet solid was added to methanolic HCl (500 ml)
  12. temperatureheated
  13. temperatureto reflux for 4 hours
  14. temperatureThe resulting mass was cooled to 0-5° C.
  15. stirringstirred for 1 hour at the same temperature
  16. filtrationThe separated solid was filtered
  17. washwashed with chilled methanol (100 ml)
  18. customdried at 60-65° C
  19. additionThe resulting solid was added to toluene (500 ml) at 25-30° C.
  20. customby purging ammonia gas slowly for 7 hours
  21. customAfter completion of the ammonia gas purging
  22. stirringthe reaction mass was stirred for 15 minutes at 25-30° C
  23. filtrationThe resulting mass was filtered
  24. distillationthe filtrate was distilled

Sources & evidence

ORD record
ord-083ee9bf27b04448a4ccc5711d2eb98f
Source dataset
uspto-grants-2016_04
Patent number
US09315456B2

Reaction notes

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