Sodium hydride → HCID 68593998, compound

HRID 383949Notes

Reaction equation

HRID 383949 reaction equation
Cl[C:2](Cl)([O:4][C:5](=[O:11])[O:6]C(Cl)(Cl)Cl)Cl.[C:13]1([C@H:19]2[CH2:24][CH2:23][CH2:22][CH2:21][C@H:20]2[NH2:25])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[H-].[Na+].[N:28]12[CH2:35][CH2:34][CH:31]([CH2:32][CH2:33]1)[CH:30]([CH2:36][OH:37])[CH2:29]2.C([O-])(O)=[O:39].[Na+]>C(Cl)Cl.C1COCC1.C(O)(=O)/C=C/C(O)=O.CCO.CCOC(C)=O.N1C=CC=CC=1>[C:5]([OH:6])(=[O:11])/[CH:31]=[CH:30]/[C:36]([OH:37])=[O:39].[C:13]1([C@H:19]2[CH2:24][CH2:23][CH2:22][CH2:21][C@H:20]2[NH:25][C:5](=[O:11])[O:4][CH2:2][CH:30]2[CH:31]3[CH2:34][CH2:35][N:28]([CH2:33][CH2:32]3)[CH2:29]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

12

Reactant 5

HCID 24758Sodium hydrideHCID 94429TriphosgeneHCID 217372HCID 217372, compoundHCID 516892Sodium BicarbonateHCID 10130010(1-Azabicyclo(2.2.2)octan-3-yl)methanol

Product 1

HCID 68593998HCID 68593998, compound

Reagents, catalysts & solvents 6

HCID 702EthanolSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 444972Fumaric AcidSolvent

Procedure

To a solution of triphosgene (362 mg) in DCM (3 mL) was added pyridine (162 mg) at 0° C., and subsequently a solution of cis-2-phenylcyclohexyl amine (300 mg) in DCM (3 mL) was added dropwise thereto, followed by stirring at room temperature for 40 minutes. To a suspension of 60% oily NaH (110 mg) in THF (1.5 mL) was added 1-azabicyclo[2.2.2]oct-3-yl methanol (363 mg) at 0° C., followed by stirring at room temperature for 20 minutes, and to the mixture was added dropwise the above-described DCM solution at 0° C., followed by stirring at 80° C. for 1 hour. To the reaction mixture 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 concentrated under reduced pressure. The residue was purified by silica gel column chromatography (CHCl3:MeOH:28% aqueous ammonia=80:10:1) to obtain a colorless oily substance (100 mg). The oily substance obtained was dissolved in a mixed solvent (EtOAc:EtOH=1:1) and fumaric acid (32 mg) was added thereto. The mixture was concentrated under reduced pressure, a mixed solvent (EtOAc:IPE) was then added thereto, and the solid precipitated was collected by filtration to obtain 1-azabicyclo[2.2.2]oct-3-ylmethyl rel-[(1R,2R)-2-phenylcyclohexyl]carbamate fumarate (103 mg) as a colorless solid.

Workup

  1. stirringby stirring at room temperature for 20 minutes
  2. stirringby stirring at 80° C. for 1 hour
  3. extractionfollowed by extraction with EtOAc
  4. washThe organic layer was washed with water and brine in this order
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (CHCl3:MeOH:28% aqueous ammonia=80:10:1)
  8. customto obtain a colorless oily substance (100 mg)
  9. customThe oily substance obtained
  10. additionwas added
  11. concentrationThe mixture was concentrated under reduced pressure
  12. additiona mixed solvent (EtOAc:IPE) was then added
  13. customthe solid precipitated
  14. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-e64328dc56a9416e8c5465dc1e849549
Source dataset
uspto-grants-2013_02
Patent number
US08367696B2

Reaction notes

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