1-Azabicyclo(2.2.2)octane-4-methanol → 1-Azabicyclo[2.2.2]oct-4-ylmethyl(5-phenyl-1,3-thiazol-4-yl)carbamate hydrochloride

HRID 383952Notes

Reaction equation

HRID 383952 reaction equation
[C:1]1([C:7]2[S:11][CH:10]=[N:9][C:8]=2C(O)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C=CC(P([N:29]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[N:32]12[CH2:39][CH2:38][C:35]([CH2:40]O)([CH2:36][CH2:37]1)[CH2:34][CH2:33]2.[C:42]([O-:45])(O)=[O:43].[Na+].[ClH:47].CCOC(C)=O>C1(C)C=CC=CC=1.CN(C=O)C.CCO>[ClH:47].[N:32]12[CH2:33][CH2:34][C:35]([CH2:40][N:29]([C:8]3[N:9]=[CH:10][S:11][C:7]=3[C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:42](=[O:43])[OH:45])([CH2:36][CH2:37]1)[CH2:38][CH2:39]2

Participants

9

Reactant 5

HCID 1413111-Azabicyclo(2.2.2)octane-4-methanolHCID 199401P,P-Diphenylphosphinic azideHCID 516892Sodium BicarbonateHCID 9448135-phenyl-1,3-thiazole-4-carboxylic AcidHCID 21866389Hydrogen chloride-ethyl acetate

Product 1

HCID 685935911-Azabicyclo[2.2.2]oct-4-ylmethyl(5-phenyl-1,3-thiazol-4-yl)carbamate hydrochloride

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-phenyl-1,3-thiazole-4-carboxylic acid (250 mg) in toluene (6 mL) were added dropwise TEA (221 μL) and DPPA (315 μL) at room temperature, followed by stirring at the same temperature for 40 minutes. Next, after stirring at 90° C. for 40 minutes, a solution of 1-azabicyclo[2.2.2]oct-4-yl methanol (241 mg) in DMF (2 mL)/toluene (2 mL) was added thereto, followed by heating under reflux for 2 hours. To the reaction liquid was added a saturated aqueous NaHCO3 solution, followed by extraction with EtOAc. The organic layer was washed with water and brine in this order, dried over MgSO4, and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by medium-pressure preparative liquid chromatography (YAMAZEN YFLC WPrep2XY, eluent; CHCl3:MeOH:28% aqueous ammonia=80:10:1) to obtain a yellow oily substance. To this solution in EtOH (2 mL) was added 4 M HCl/EtOAc (1 mL) at room temperature, followed by stirring, and the solvent was concentrated under reduced pressure. The residue obtained was recrystallized from EtOH/ether to obtain 1-azabicyclo[2.2.2]oct-4-ylmethyl(5-phenyl-1,3-thiazol-4-yl)carbamate hydrochloride (145 mg) as a yellow solid.

Workup

  1. stirringNext, after stirring at 90° C. for 40 minutes
  2. temperatureby heating
  3. temperatureunder reflux for 2 hours
  4. customTo the reaction liquid
  5. extractionfollowed by extraction with EtOAc
  6. washThe organic layer was washed with water and brine in this order
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified by medium-pressure preparative liquid chromatography (YAMAZEN YFLC WPrep2XY, eluent; CHCl3:MeOH:28% aqueous ammonia=80:10:1)
  11. customto obtain a yellow oily substance
  12. stirringby stirring
  13. concentrationthe solvent was concentrated under reduced pressure
  14. customThe residue obtained
  15. customwas recrystallized from EtOH/ether

Sources & evidence

ORD record
ord-a2c76768b18146f9aa68e7fececbfdfd
Source dataset
uspto-grants-2013_02
Patent number
US08367696B2

Reaction notes

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