Toluene → (1S,4S)-5-(5-Benzoyl-3-pyridyl)-2-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]heptane

HRID 2354468Notes

Reaction equation

HRID 2354468 reaction equation
[C:1]([C:9]1[CH:10]=[N:11][CH:12]=[C:13](Br)[CH:14]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:16]([O:20][C:21]([N:23]1[CH2:28][C@@H:27]2[CH2:29][C@H:24]1[CH2:25][NH:26]2)=[O:22])([CH3:19])([CH3:18])[CH3:17].CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([C:9]1[CH:14]=[C:13]([N:26]2[CH2:25][C@@H:24]3[CH2:29][C@H:27]2[CH2:28][N:23]3[C:21]([O:20][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:22])[CH:12]=[N:11][CH:10]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 796643(5-Bromopyridin-3-yl)(phenyl)methanoneHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 23676156Sodium t-butoxide

Product 1

HCID 68457814(1S,4S)-5-(5-Benzoyl-3-pyridyl)-2-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]heptaneYield 48%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Procedure

In a sealed pressure tube under a nitrogen atmosphere, 3-benzoyl-5-bromopyridine (0.542 g, 2.1 mmol), (1S,4S)-N-(tert-butoxycarb- onyl)-2,5-diazabicyclo[2.2.1]heptane (0.475 g, 2.4 mmol), tris (dibenzylideneacetone)dipalladium (0) (0.04 g, 0.04 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.05 g, 0.08 mmol), sodium tert-butoxide (0.380 g, 3.8 mmol) and anhydrous toluene (20 mL) were stirred at 90° C. for 20 h. The reaction mixture was cooled to room temperature and diluted with water (200 mL) and then extracted with diethyl ether (100 mL). The diethyl ether extract was dried (MgSO4), filtered and concentrated by rotary evaporation. The residue was purified by flash chromatography on silica gel, using a gradient of 50% to 80% ethyl acetate:hexane as eluent, to yield 0.364 g (48%) of a yellow oil.

Workup

  1. extractionextracted with diethyl ether (100 mL)
  2. extractionThe diethyl ether extract
  3. dry with materialwas dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-77dd0e530c9443c8929cc499526e01d5
Source dataset
uspto-grants-2010_07
Patent number
USRE041439E1

Reaction notes

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