Hydrochloric Acid → HCID 19800164, compound

HRID 1646939Notes

Reaction equation

HRID 1646939 reaction equation
CC1(C)CCCC(C)(C)N1.C([Li])CCC.[Cl:16][C:17]1[CH:22]=[N:21][CH:20]=[CH:19][N:18]=1.[N:23]12[CH2:29][CH:26]([CH2:27][CH2:28]1)[C:25](=[O:30])[CH2:24]2.Cl>C1COCC1.CCCCCC.C(O)C>[Cl:16][C:17]1[C:22]([C:25]2([OH:30])[CH:26]3[CH2:29][N:23]([CH2:28][CH2:27]3)[CH2:24]2)=[N:21][CH:20]=[CH:19][N:18]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 130352,2,6,6-TetramethylpiperidineHCID 73277ChloropyrazineHCID 108554071-Azabicyclo[2.2.1]heptan-3-oneHCID 178418339Butyllithium

Product 1

HCID 19800164HCID 19800164, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Procedure

A solution of 7.2 ml of 2,2,6,6-tetramethylpiperidine in 300 ml of THF was cooled to -5° C. as 25 ml of 1.6M butyllithium (0.04 mol) in hexane was added dropwise. The reaction was stirred 10 min then cooled to -77° C. as 3 ml of 2-chloropyrazine in 7 ml of THF was added dropwise. After another 15 min, 4.4 g of 1-azabicyclo[2.2.1]heptan-3-one (0.0396 mol) in 10 ml of THF was added and the reaction stirred 1 h. A solution of 8 ml of conc. HCl in 4 ml of ethanol was added and the cooling was removed. When the temperature reached -10° C., 100 ml of water was added, the organics were evaporated, and the residue treated with 11 ml of 5N NaOH. The solvent was reduced to a small volume, ca. 50 ml, the mixture cooled in ice-water, and the solid collected by filtration. The aqueous fraction was extracted 3× with 50 ml of CHCl3, the extracts added to the solid filtrate, and the total volume of the mixture taken to 500 ml with more CHCl3. The mixture was heated to boiling, dried, filtered, and the solvent evaporated to give a brown solid. The solid was recrystallized from isopropanol to give 4.1 g of tan crystalline (26), mp 220° C. dec. NMR ppm (CDCl3) 1.55-1.9 (2H, m), 2.27 (1H, m), 2.42-2.58 (2H, m), 2.75 (2H, m), 2.95 (1H, m), 3.5 (1H, d) 3.6 (1H, d), 8.3 (1H, d) 8.42 (1H, d). Anal. C10H12ClN3O requires C: 53.22; H: 5.36; N: 18.62%. Found C: 53.10; H: 5.20; N: 18.41%.

Workup

  1. additionwas added dropwise
  2. additionwas added dropwise
  3. waitAfter another 15 min
  4. stirringthe reaction stirred 1 h
  5. customthe cooling was removed
  6. customreached -10° C.
  7. addition100 ml of water was added
  8. customthe organics were evaporated
  9. additionthe residue treated with 11 ml of 5N NaOH
  10. temperaturethe mixture cooled in ice-water
  11. filtrationthe solid collected by filtration
  12. extractionThe aqueous fraction was extracted 3× with 50 ml of CHCl3
  13. additionthe extracts added to the solid filtrate
  14. temperatureThe mixture was heated
  15. customdried
  16. filtrationfiltered
  17. customthe solvent evaporated
  18. customto give a brown solid
  19. customThe solid was recrystallized from isopropanol

Sources & evidence

ORD record
ord-869e02600db74ee69dcfe2dc017593dd
Source dataset
uspto-grants-1993_01
Patent number
US05182283

Reaction notes

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