Sodium Bicarbonate → (E)-5-bromo-alpha-[2-(3,4-dichlorophenyl)ethenyl]-2-methoxy-3-pyridinemethanol

HRID 280189Notes

Reaction equation

HRID 280189 reaction equation
Br[C:2]1[C:3]([O:9][CH3:10])=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.C([Li])CCC.CCCCCC.[Cl:22][C:23]1[CH:24]=[C:25]([CH:30]=[CH:31][C:32]=1[Cl:33])[CH:26]=[CH:27][CH:28]=[O:29].C(=O)(O)[O-].[Na+]>CCOCC.O1CCCC1>[Br:8][C:6]1[CH:7]=[C:2]([CH:28](/[CH:27]=[CH:26]/[C:25]2[CH:30]=[CH:31][C:32]([Cl:33])=[C:23]([Cl:22])[CH:24]=2)[OH:29])[C:3]([O:9][CH3:10])=[N:4][CH:5]=1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 135677523,5-Dibromo-2-methoxypyridineHCID 538805763,4-DichlorocinnamaldehydeHCID 178418244HCID 178418244, compound

Product 1

HCID 13567755(E)-5-bromo-alpha-[2-(3,4-dichlorophenyl)ethenyl]-2-methoxy-3-pyridinemethanol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 60.6 g of 3,5-dibromo-2-methoxypyridine in 900 ml of anhydrous ether was stirred under nitrogen and cooled to -78° C. to give a thick slurry. Efficient stirring was used to prevent the solid starting material from adhering to the wall of the reaction vessel. While the temperature was maintained below -65° C., 85 ml of 2.67M n-butyllithium/hexane was added dropwise. The reaction mixture was homogeneous upon completion of the addition and it was stirred for 15 minutes at -78° C. Then, a solution of 45.6 g of 3,4-dichlorocinnamaldehyde in 200 ml of anhydrous tetrahydrofuran was added dropwise while keeping the temperature below -65° C. When the addition was complete, 100 ml of aqueous saturated sodium bicarbonate solution was added to the cold reaction mixture. It was then allowed to warm to about -40° C. and then partitioned between ether and aqueous saturated sodium bicarbonate solution. The aqueous layer was extracted with ether and the combined ether layers were washed with aqueous saturated sodium chloride solution, dried over potassium carbionate, filtered and concentrated to leave a pale yellow solid. This was recrystallized from a mixture of 2-propanol/ethyl acetate/hexane (1:3:5) to give (E)-5-bromo-α-[2-(3,4-dichlorophenyl)ethenyl]-2-methoxy-3-pyridinemethanol melting at about 149°-150° C.

Workup

  1. customto give a thick slurry
  2. temperatureWhile the temperature was maintained below -65° C.
  3. additionThe reaction mixture was homogeneous upon completion of the addition and it
  4. stirringwas stirred for 15 minutes at -78° C
  5. customthe temperature below -65° C
  6. additionWhen the addition
  7. temperatureto warm to about -40° C.
  8. custompartitioned between ether and aqueous saturated sodium bicarbonate solution
  9. extractionThe aqueous layer was extracted with ether
  10. washthe combined ether layers were washed with aqueous saturated sodium chloride solution
  11. dry with materialdried over potassium carbionate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto leave a pale yellow solid
  15. customThis was recrystallized from a mixture of 2-propanol/ethyl acetate/hexane (1:3:5)

Sources & evidence

ORD record
ord-f4b305f9ebaf46389395a4decc4f1a00
Source dataset
uspto-grants-1986_05
Patent number
US04588733

Reaction notes

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