Hydrochloric Acid → N-(3,4-dichlorophenyl)-4-(pyrrolidin-3-ylmethyl)piperazine-1-carboxamide

HRID 2371163Notes

Reaction equation

HRID 2371163 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]([CH:20]3[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21]3)=O)[CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8].B.Cl>C1COCC1.CO>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][CH:20]3[CH2:24][CH2:23][NH:22][CH2:21]3)[CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 6331BoraneHCID 57656707Tert-butyl 3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)carbonyl]pyrrolidine-1-carboxylate

Product 1

HCID 57656782N-(3,4-dichlorophenyl)-4-(pyrrolidin-3-ylmethyl)piperazine-1-carboxamideYield 17.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of tert-butyl 3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)carbonyl]pyrrolidine-1-carboxylate (3.39 g, 7.19 mmol) in THF (60 ml) was added a 1M solution of borane in THF (21.6 ml, 21.6 mmol) and the reaction heated to reflux for 4 hours. The cooled reaction mixture was then cautiously quenched by addition of methanol then solvents removed in vacuo to give a white solid. To this was then added saturated HCl in methanol (150 ml) and heated to reflux for 1 hour. The reaction mixture was then evaporated to dryness, partitioned between 2M NaOH and DCM, extracted twice, combined organics dried (Na2SO4), filtered and evaporated to a colorless oil. This was then purified on Isco™ Companion (40 g column: 20% methanolic ammonia/DCM) to give the product N-(3,4-dichlorophenyl)-4-(pyrrolidin-3-ylmethyl)piperazine-1-carboxamide as a white foam (444 mg, 1.24 mmol, 17%).

Workup

  1. temperaturethe reaction heated
  2. temperatureto reflux for 4 hours
  3. customThe cooled reaction mixture
  4. customwas then cautiously quenched by addition of methanol
  5. customsolvents removed in vacuo
  6. customto give a white solid
  7. temperatureto reflux for 1 hour
  8. customThe reaction mixture was then evaporated to dryness
  9. custompartitioned between 2M NaOH and DCM
  10. extractionextracted twice
  11. dry with materialcombined organics dried (Na2SO4)
  12. filtrationfiltered
  13. customevaporated to a colorless oil
  14. customThis was then purified on Isco™ Companion (40 g column: 20% methanolic ammonia/DCM)

Sources & evidence

ORD record
ord-136767893b8d4cab8b530dc7026c0db1
Source dataset
uspto-grants-2014_04
Patent number
US08710224B2

Reaction notes

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