3-Bromo-5-ethoxypyridine → 1-Benzyl-7-(5-ethoxypyridin-3-yl)-1,7-diazaspiro[4.4]nonane

HRID 967928Notes

Reaction equation

HRID 967928 reaction equation
[CH2:1]([N:8]1[C:12]2([CH2:16][CH2:15][NH:14][CH2:13]2)[CH2:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:18]1[CH:19]=[N:20][CH:21]=[C:22]([O:24][CH2:25][CH3:26])[CH:23]=1.CC(C)([O-])C.[K+]>C1(C)C=CC=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.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>[CH2:1]([N:8]1[C:12]2([CH2:16][CH2:15][N:14]([C:18]3[CH:19]=[N:20][CH:21]=[C:22]([O:24][CH2:25][CH3:26])[CH:23]=3)[CH2:13]2)[CH2:11][CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 122934803-Bromo-5-ethoxypyridineHCID 156347131-Benzyl-1,7-diazaspiro(4.4)nonaneHCID 23665647Potassium tert-butoxide

Product 1

HCID 222912451-Benzyl-7-(5-ethoxypyridin-3-yl)-1,7-diazaspiro[4.4]nonaneYield 69%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

1-Benzyl-1,7-diazaspiro[4.4]nonane (500.0 mg, 2.4 mmol) was dissolved in dry toluene (15 mL) in a 50 mL round bottom flask equipped with a magnetic stirring bar. Nitrogen was bubbled through the solution in a slow stream. To the stirring solution was added 3-bromo-5-ethoxypyridine (513.8 mg, 2.55 mmol), potassium tert-butoxide (1039.0 mg, 9.26 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (86.4 mg, 0.14 mmol) and tris(dibenzylideneacetone)dipalladium(0) (63.6 mg, 0.06 mmol), while continuing to purge with nitrogen. Nitrogen flow was discontinued and the flask was sealed and heated at 90° C. for 8 h. The reaction was cooled and the solvent was removed by rotary evaporation. The resulting residue was suspended in saturated aqueous sodium bicarbonate (10 mL) and extracted with chloroform (4×25 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated by rotary evaporation to a thick dark mass. Purification by column chromatography, using methanol/chloroform (2:98, v/v) as the eluent, gave 0.54 g of the desired compound as a light brown viscous liquid (69%).

Workup

  1. customequipped with a magnetic stirring bar
  2. customNitrogen was bubbled through the solution in a slow stream
  3. customto purge with nitrogen
  4. customthe flask was sealed
  5. temperatureThe reaction was cooled
  6. customthe solvent was removed by rotary evaporation
  7. extractionextracted with chloroform (4×25 mL)
  8. dry with materialThe combined organic extracts were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated by rotary evaporation to a thick dark mass
  11. customPurification by column chromatography

Sources & evidence

ORD record
ord-45ad2ad38fe04e60ab998554c11e918e
Source dataset
uspto-grants-2005_10
Patent number
US06956042B2

Reaction notes

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