Sodium Chloride → 3-Methyl-6-dimethylaminopyridine-2-carbaldehyde

HRID 376302Notes

Reaction equation

HRID 376302 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].[CH3:6][N:7](C)[CH2:8]CNC.Cl[C:14]1[N:19]=[C:18]([CH:20]=[O:21])C=CC=1.CN(C)CCN(C)C.CI.[Cl-].[Na+]>CCCCCC.O1CCCC1>[CH3:4][C:3]1[C:18]([CH:20]=[O:21])=[N:19][C:14]([N:7]([CH3:8])[CH3:6])=[CH:1][CH:2]=1

Participants

9

Reactant 6

HCID 5234Sodium ChlorideHCID 6328Methyl iodideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 673381,2-Ethanediamine, N1,N1,N2-trimethyl-HCID 107968486-Chloro-2-pyridinecarboxaldehydeHCID 178418339Butyllithium

Product 1

HCID 193617593-Methyl-6-dimethylaminopyridine-2-carbaldehyde

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent2×

Conditions

Temperature
-60 °C

Procedure

2.65 ml of a 1.6 M solution of n-butyllithium in hexane are introduced into a solution of 0.53 ml of N,N,N'-trimethylethylenediamine (4.24 mmol) and 10 ml of tetrahydrofuran cooled to -60° C. The solution is stirred for 15 minutes at -40° C. and then it is cooled to -70° C. and a solution of 0.50 g of 6-chloropyridine-2-carbaldehyde (3.53 mmol) and 4 ml of tetrahydrofuran is introduced dropwise. The orange-colored solution is stirred for 30 minutes at -70° C. and then 1.28 ml of tetramethylethylenediamine (8.48 mmol) are introduced and then after 10 minutes 5.30 ml of a 1.6M solution of n-butylithium in hexane are introduced. The brown solution is stirred for 2 hours at -78° C. and 1.50 ml of methyl iodide (25 mmol) are added dropwise. After stirring for one hour at -78° C. and then for 10 minutes at 20° C., the reaction mixture is poured into a saturated aqueous solution of sodium chloride and extracted with ethyl acetate. The organic phase is washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered and the solvent evaporated off. 0.23 g of the title product is recovered after purification by chromatography on a silica column (eluent: hexane/ethyl acetate; 95:5).

Workup

  1. temperatureit is cooled to -70° C.
  2. stirringThe orange-colored solution is stirred for 30 minutes at -70° C.
  3. stirringThe brown solution is stirred for 2 hours at -78° C.
  4. stirringAfter stirring for one hour at -78° C.
  5. waitfor 10 minutes at 20° C.
  6. extractionextracted with ethyl acetate
  7. washThe organic phase is washed with a saturated aqueous solution of sodium chloride
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. customthe solvent evaporated off
  11. custom0.23 g of the title product is recovered
  12. customafter purification by chromatography on a silica column (eluent: hexane/ethyl acetate; 95:5)

Sources & evidence

ORD record
ord-b4e9d249d87e48f09cf29fa6bdc03b02
Source dataset
uspto-grants-2000_02
Patent number
US06020345

Reaction notes

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