2,6-Dibromopyridine → HCID 58629909, compound

HRID 1391768Notes

Reaction equation

HRID 1391768 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([Br:13])[N:8]=1.C(N(CC1C=CC=CC=1)[C:17](=[O:22])[CH2:18][CH2:19][O:20][CH3:21])C>C1COCC1>[Br:13][C:9]1[N:8]=[C:7]([C:17](=[O:22])[CH2:18][CH2:19][O:20][CH3:21])[CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 122742,6-DibromopyridineHCID 58629837HCID 58629837, compoundHCID 178418339Butyllithium

Product 1

HCID 58629909HCID 58629909, compoundYield 34.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of n-Butyllithium (1.6M in hexanes, 4.06 mL, 6.50 mmol) in anhydrous THF (4.0 mL) under nitrogen at −78° C. was added a solution of 2,6-dibromopyridine (1.54 g, 6.50 mmol) in anhydrous THF (9.5 mL) drop-wise over 45 min. The resulting dark green solution was stirred at −78° C. for 15 min and then treated with N-ethyl-3-(methyloxy)-N-(phenylmethyl)propanamide (2.16 g, 9.76 mmol), washing in with anhydrous THF (3.0 mL). The resulting green solution was stirred at −78° C. for 15 min and was then treated with a solution of AcOH (0.40 mL) in MeOH (6.60 mL) to give a pale brown solution. This mixture was removed from the cooling bath and allowed to warm to room temperature, then stirred for 2 h. The mixture was then treated with saturated aqueous. NH4Cl (40 mL) and the products extracted with EtOAc (2×50 mL). The combined organic layer was then washed with brine (60 mL), dried (MgSO4) and the reduced in vacuo to give an orange oil. Purification by Biotage (silica, 90 g cartridge) eluting with cyclohexane:EtOAc (10:1) afforded the title compound as a white solid (547 mg).

Workup

  1. washwashing in with anhydrous THF (3.0 mL)
  2. stirringThe resulting green solution was stirred at −78° C. for 15 min
  3. additionwas then treated with a solution of AcOH (0.40 mL) in MeOH (6.60 mL)
  4. customto give a pale brown solution
  5. customThis mixture was removed from the cooling bath
  6. temperatureto warm to room temperature
  7. stirringstirred for 2 h
  8. additionThe mixture was then treated with saturated aqueous
  9. extractionNH4Cl (40 mL) and the products extracted with EtOAc (2×50 mL)
  10. washThe combined organic layer was then washed with brine (60 mL)
  11. dry with materialdried (MgSO4)
  12. customto give an orange oil
  13. customPurification by Biotage (silica, 90 g cartridge)
  14. washeluting with cyclohexane:EtOAc (10:1)

Sources & evidence

ORD record
ord-fc2f907188b5476ab2a5d731df9fb372
Source dataset
uspto-grants-2008_03
Patent number
US07338960B2

Reaction notes

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