Dimethylformamide → 6-Isopropoxypicolinaldehyde

HRID 1641320Notes

Reaction equation

HRID 1641320 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH:9]([CH3:11])[CH3:10])[N:3]=1.C([Li])CCC.CN([CH:20]=[O:21])C>C1COCC1>[CH:9]([O:8][C:4]1[N:3]=[C:2]([CH:20]=[O:21])[CH:7]=[CH:6][CH:5]=1)([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 221807682-Bromo-6-isopropoxypyridineHCID 178418339Butyllithium

Product 1

HCID 450910446-Isopropoxypicolinaldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

6-isopropoxypyridine-2-carbaldehyde was prepared in a manner similar to that described in D. L. Comins, M. O. Killpack, J. Org. Chem. 1990 55 69-73 for the methoxy analog. 2-bromo-6-isopropoxypyridine (1 g, 4.6 mmole) was dissolved in 10 ml dry THF under argon, cooled to −78° C. and treated with added 2.5 M n-Butyl lithium (1.9 mL, 4.8 mmole) keeping the temperature of the reaction below −65° C. After the reaction had stirred 45 min DMF (0.717 mL, 9.25 mmole) was added, again keeping temp below −60° C., the reaction was stirred for 15 min, then quenched with saturated bicarbonate solution. The layers were separated, the aqueous extracted with CHCl3, the organic layers dried over Na2SO4, filtered and evap carefully, and the residue chromatographed in 0-50% Ether/hexanes to give the product as an oil. LCMS (m+1)=165.2

Workup

  1. additiontreated
  2. customthe temperature of the reaction below −65° C
  3. additionwas added
  4. customagain keeping temp below −60° C.
  5. customquenched with saturated bicarbonate solution
  6. customThe layers were separated
  7. extractionthe aqueous extracted with CHCl3
  8. dry with materialthe organic layers dried over Na2SO4
  9. filtrationfiltered
  10. customthe residue chromatographed in 0-50% Ether/hexanes

Sources & evidence

ORD record
ord-780d416e747548d4b3f3a4c5eb789f70
Source dataset
uspto-grants-2012_02
Patent number
US08114887B2

Reaction notes

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