Diiodomethane → tert-butyl 6-[(benzyloxy)methyl]-3-azabicyclo[4.I.0]heptane-3-carboxylate

HRID 70788Notes

Reaction equation

HRID 70788 reaction equation
[CH2:1]([Zn]CC)C.C(O)(C(F)(F)F)=O.ICI.[CH2:16]([O:23][CH2:24][C:25]1[CH2:26][CH2:27][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:29][CH:30]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.[Cl-].[NH4+]>C(N(CC)CC)C.ClCCl>[CH2:16]([O:23][CH2:24][C:25]12[CH2:1][CH:26]1[CH2:27][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:29][CH2:30]2)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

9

Reactant 6

HCID 6346DiiodomethaneHCID 6422Trifluoroacetic acidHCID 25517Ammonium ChlorideHCID 90495Di-tert-butyl dicarbonateHCID 71268696HCID 71268696, compoundHCID 178418750HCID 178418750, compound

Product 1

HCID 71270575tert-butyl 6-[(benzyloxy)methyl]-3-azabicyclo[4.I.0]heptane-3-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent4×HCID 8471TriethylamineSolvent

Procedure

Under an argon atmosphere, after diethyl zinc (1.0M hexane solution: 27.0 ml) was added to dichloromethane (40 ml) with ice cooling, a TFA (2 ml)/dichloromethane (10 ml) solution was added dropwise, and stirring was performed under ice cooling for 40 minutes. Then, after a diiodomethane (7.24 g)/dichloromethane (10 ml) solution was added dropwise and further stirring was performed at the same temperature for 40 minutes. Tert-butyl 4-[(benzyloxy)methyl]-3,6-dihydropyridine-1(2H)-carboxylate (3.28 g)/dichloromethane (30 ml) solution was added dropwise, and stirring was performed at room temperature for 15 hours. After adding triethylamine under ice cooling and adjusting pH to 7 to 8, di-tert-butyl dicarbonate (2.83 g) was added, and stirring was performed at room temperature for 5 hours. A saturated ammonium chloride aqueous solution was added, extraction was performed with chloroform, followed by washing with saturated brine and drying over anhydrous magnesium sulfate. The residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (EtOAc/hexane) to obtain tert-butyl 6-[(benzyloxy)methyl]-3-azabicyclo[4.I.0]heptane-3-carboxylate (2.22 g).

Workup

  1. stirringfurther stirring
  2. waitwas performed at the same temperature for 40 minutes
  3. stirringstirring
  4. waitwas performed at room temperature for 15 hours
  5. additionwas added
  6. stirringstirring
  7. waitwas performed at room temperature for 5 hours
  8. extractionextraction
  9. washby washing with saturated brine
  10. dry with materialdrying over anhydrous magnesium sulfate
  11. customThe residue obtained by concentration under reduced pressure
  12. customwas purified by silica gel column chromatography (EtOAc/hexane)

Sources & evidence

ORD record
ord-b2b79ce0d70b4c4092c7180eb9b61e2e
Source dataset
uspto-grants-2014_09
Patent number
US08822688B2

Reaction notes

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