Triethylamine → tert-Butyl (3-benzyl-3-azabicyclo[3.1.0]hexan-6-yl)carbamate

HRID 54713Notes

Reaction equation

HRID 54713 reaction equation
C(N1[CH2:13][CH:12]2[CH:10]([CH:11]2C(O)=O)C1)C1C=CC=CC=1.[CH2:17]([N:24]1[CH2:29][CH:28]2[CH:26]([CH:27]2C(OCC)=O)[CH2:25]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[OH-:35].[Na+].C([N:39]([CH2:42]C)CC)C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:51])=CC=1>O.C(O)(C)(C)C>[CH2:17]([N:24]1[CH2:25][CH:26]2[CH:28]([CH:27]2[NH:39][C:42]([O:51][C:12]([CH3:11])([CH3:10])[CH3:13])=[O:35])[CH2:29]1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 199401P,P-Diphenylphosphinic azideHCID 109769003-benzyl-3-azabicyclo[3.1.0]hexane-6-carboxylic AcidHCID 15818457Ethyl 3-benzyl-3-azabicyclo[3.1.0]hexane-6-carboxylate

Product 1

HCID 9860737tert-Butyl (3-benzyl-3-azabicyclo[3.1.0]hexan-6-yl)carbamateYield 31%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6386tert-ButanolSolvent

Procedure

A mixture of 3-benzyl-3-azabicyclo[3.1.0]hexane-6-carboxylic acid (116 mg, 0.53 mmol) obtained by treating ethyl 3-benzyl-3-azabicyclo[3.1.0]hexane-6-carboxylate obtained in step 5 of Example 1, with an aqueous solution of NaOH, with triethylamine (239 mg, 2.36 mmol), DPPA (303 mg, 1.10 mmol) and t-butanol (4 ml), was heated under reflux in a nitrogen atmosphere for 19 hours, followed by cooling the reaction mixture, pouring it into water, extracting with toluene, washing the organic layer successively with an aqueous solution of Na2CO3, water and a saturated aqueous solution of NaCl, drying over anhydrous magnesium sulfate, distilling off the solvent under reduced pressure and purifying the residue according to thin-layer chromatography (developing solvent: chloroform:methanol=20:1), to obtain 3-benzyl-6-t-butoxycarbonylamino-3-azabicyclo[3.1.0]hexane (47 mg, 0.16 mmol, 31%).

Workup

  1. customobtained
  2. temperatureunder reflux in a nitrogen atmosphere for 19 hours
  3. temperatureby cooling the reaction mixture
  4. extractionextracting with toluene
  5. washwashing the organic layer successively with an aqueous solution of Na2CO3, water
  6. dry with materiala saturated aqueous solution of NaCl, drying over anhydrous magnesium sulfate
  7. distillationdistilling off the solvent under reduced pressure
  8. custompurifying the residue

Sources & evidence

ORD record
ord-93f82efbd2724d1aa10420fc76ad47ba
Source dataset
uspto-grants-1997_04
Patent number
US05623078

Reaction notes

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