Pyridine → 5-chloro-6-methyl-3-Pyridinecarboxaldehyde

HRID 420760Notes

Reaction equation

HRID 420760 reaction equation
N1C=CC=CC=1.[Cl:7][C:8]1[CH:9]=[C:10]([CH2:15][OH:16])[CH:11]=[N:12][C:13]=1[CH3:14].C(N(CC)C(C)C)(C)C>CS(C)=O.C(Cl)Cl>[Cl:7][C:8]1[CH:9]=[C:10]([CH:15]=[O:16])[CH:11]=[N:12][C:13]=1[CH3:14]

Participants

6

Reactant 3

HCID 1049PyridineHCID 81531DiisopropylethylamineHCID 58001770(5-Chloro-6-methylpyridin-3-yl)methanol

Product 1

HCID 580017625-chloro-6-methyl-3-PyridinecarboxaldehydeYield 88%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Sulphur trioxide pyridene complex (1010 mg, 6.35 mmol) was suspended in dry DMSO (1.126 ml, 15.87 mmol). Then pyridine (0.513 ml, 6.35 mmol) was added and after 15 min under stirring, this solution was slowly added to other containing a mixture of (5-chloro-6-methyl-3-pyridinyl)methanol (for a synthesis see WO2006/137485 A1 Example 255) (500 mg, 3.17 mmol) and N,N-diisopropylethylamine (1.939 ml, 11.10 mmol) in a mixture of DMSO (1.12 ml) and DCM (4 ml) at 0° C. After 1 h under stirring, the ice bath was removed and the reaction was left at room temperature overnight. DCM was evaporated under vacuum, H2O and Et2O (1:1) were added and the aqueous layer was extracted several times with Et2O. Organic layers were washed with brine, dried (Na2SO4), filtered and concentrated to afford 5-chloro-6-methyl-3-pyridinecarbaldehyde (435 mg, 88%) as a yellow solid.

Workup

  1. additionthis solution was slowly added
  2. additionto other containing
  3. stirringAfter 1 h under stirring
  4. customthe ice bath was removed
  5. customDCM was evaporated under vacuum, H2O and Et2O (1:1)
  6. additionwere added
  7. extractionthe aqueous layer was extracted several times with Et2O
  8. washOrganic layers were washed with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-0bdce8063ab749678ae396f3066d81d0
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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