Cesium fluoride → 3-(8-Benzyl-8-azabicyclo[3.2.1]oct-2-en-3-yl)benzamide

HRID 445952Notes

Reaction equation

HRID 445952 reaction equation
[CH2:1]([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH:10]=[C:11](OS(C1C=CC(C)=CC=1)(=O)=O)[CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:27]([C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1)(=[O:29])[NH2:28].[F-].[Cs+]>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)CCCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH:10]=[C:11]([C:34]1[CH:35]=[C:30]([CH:31]=[CH:32][CH:33]=1)[C:27]([NH2:28])=[O:29])[CH2:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 2737814(3-Carbamoylphenyl)boronic acidHCID 86626444Toluene-4-sulfonic acid 8-benzyl-8-azabicyclo[3.2.1]oct-2-en-3-yl ester

Product 1

HCID 671012843-(8-Benzyl-8-azabicyclo[3.2.1]oct-2-en-3-yl)benzamideYield 64.4%

Reagents, catalysts & solvents 2

HCID 27334141,5-Bis(diphenylphosphino)pentaneCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

To a 100 mL round bottom flask was added toluene-4-sulfonic acid 8-benzyl-8-azabicyclo[3.2.1]oct-2-en-3-yl ester (0.75 g, 2 mmol), 3-carbamoylphenyl boronic acid (0.36 g, 2.2 mmol), Pd2dba3 (0.055 g, 0.06 mmol), 1,5-bis(diphenylphosphino)pentane (0.053 g, 0.12 mmol) and CsF (0.91, 6 mmol). The reaction mixture was purged with nitrogen for 5 min, and THF (8 mL)and 1.5 mL DMF (1.5 mL) were added. The suspension was stirred at room temperature and purged with nitrogen for another 5 min, then heated to 68° C. After 21 h at 68° C., the reaction mixture was cooled to room temperature and partitioned between EtOAc (20 mL) and 1 N NaOH (20 mL). The organic layer was washed with 1:1 brine:water (2×20 mL) and dried over Na2SO4. The organic layer was concentrated to 7 to 8 mL, resulting in a slurry that was filtered to provide the title compound (0.41 g, 64% yield) as off-White solids. (m/z): [M+H]+ calcd for C21H22N2O, 319.18; found 319.4.

Workup

  1. customThe reaction mixture was purged with nitrogen for 5 min
  2. additionTHF (8 mL)and 1.5 mL DMF (1.5 mL) were added
  3. custompurged with nitrogen for another 5 min
  4. temperatureheated to 68° C
  5. temperaturethe reaction mixture was cooled to room temperature
  6. custompartitioned between EtOAc (20 mL) and 1 N NaOH (20 mL)
  7. washThe organic layer was washed with 1:1 brine
  8. dry with materialwater (2×20 mL) and dried over Na2SO4
  9. concentrationThe organic layer was concentrated to 7 to 8 mL
  10. customresulting in a slurry that
  11. filtrationwas filtered

Sources & evidence

ORD record
ord-e856a7bca0c9424582a25485c2b7ac52
Source dataset
uspto-grants-2013_07
Patent number
US08476440B2

Reaction notes

Loading…