3,5-Dibromopyridine → HCID 67297729, compound

HRID 241599Notes

Reaction equation

HRID 241599 reaction equation
[Si]([O:18][CH2:19][CH:20]1[NH:24][C:23](=O)[CH2:22][CH2:21]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[Br:26][C:27]1[CH:28]=[N:29][CH:30]=[C:31](Br)[CH:32]=1.[CH3:34]C(C)([O-])C.[Na+].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>O1CCOCC1.C(=O)(O)[O-].[Na+].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]>[Br:26][C:27]1[CH:32]=[C:31]([N:24]2[CH:20]([CH2:19][OH:18])[CH2:21][CH:22]3[CH:23]2[CH2:34]3)[CH:30]=[N:29][CH:28]=1

Participants

8

Reactant 4

HCID 693693,5-DibromopyridineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 580115465-(tert-Butyldiphenylsiloxymethyl)pyrrolidine-2-one

Product 1

HCID 67297729HCID 67297729, compoundYield 33%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred solution of (2-Azabicyclo[3.1.0]hex-3-yl)methanol (750 mg, 6.63 mmol) (obtained in step (i)) in dry 1,4-dioxan (20 mL) in a pressure reaction vessel was added 3,5-dibromopyridine (1.57 grams, 6.63 mmol), sodium tert-butoxide (700 mg, 7.3 mmol) and racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (207 mg, 0.33 mmol). The reaction mixture was degassed for 30 minutes, then tris(dibenzylideneacetone)dipalladium (0) (122 mg, 0.133 mmol) was added. The screw cap was fixed on the reaction vessel, the temperature of the reaction was gradually increased to 110° C. and the reaction mixture was stirred at this temperature for 16 hours. The reaction mixture was cooled to room temperature diluted with saturated sodium bicarbonate and extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure and the crude product was purified by 230-400 silica gel flash column chromatography to obtain title compound of 600 mg as solid. Yield: 33%.

Workup

  1. customThe reaction mixture was degassed for 30 minutes
  2. customThe screw cap
  3. temperatureThe reaction mixture was cooled to room temperature
  4. extractionextracted with ethyl acetate
  5. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customthe crude product was purified by 230-400 silica gel flash column chromatography

Sources & evidence

ORD record
ord-e28703a6b21743028431e44ce439ac68
Source dataset
uspto-grants-2014_02
Patent number
US08653071B2

Reaction notes

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