Acetone → 5-Chloro-6-(hydroxymethyl)-3-pyridinecarbaldehyde

HRID 420728Notes

Reaction equation

HRID 420728 reaction equation
C(O)(=O)C(O)=O.[Cl:7][C:8]1[C:9]([CH2:19][OH:20])=[N:10][CH:11]=[C:12]([CH:14]2OCC[O:15]2)[CH:13]=1.CC(C)=O.[OH-].[Na+]>O>[Cl:7][C:8]1[CH:13]=[C:12]([CH:14]=[O:15])[CH:11]=[N:10][C:9]=1[CH2:19][OH:20]

Participants

6

Reactant 4

HCID 180AcetoneHCID 971Oxalic AcidHCID 14798Sodium HydroxideHCID 66658029HCID 66658029, compound

Product 1

HCID 580017855-Chloro-6-(hydroxymethyl)-3-pyridinecarbaldehydeYield 10%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Oxalic acid (415 mg, 3.29 mmol) was added to a mixture of [3-chloro-5-(1,3-dioxolan-2-yl)-2-pyridinyl]methanol (142 mg, 0.659 mmol), acetone (7.5 ml), and water (7.5 ml) at room temperature and heated under reflux. After 2.5 h, HPLC showed full conversion. Cooled to rt, basified with 1M NaOH, extracted with TBME, dried (MgSO4), filtered and concentrated to give 139 mg of crude material. Purification by flash chromatography using Flashmaster II, a 5 g silica gel cartridge, and mixtures of DCM and MeOH as eluent afforded impure product. Repurification by manual flash chromatography using a 1 g silica gel cartridge, and mixtures of hexane and EtOAc as eluent afforded 5-chloro-6-(hydroxymethyl)-3-pyridinecarbaldehyde (11.3 mg, 10%) as a white solid.

Workup

  1. temperatureheated
  2. temperatureunder reflux
  3. extractionextracted with TBME
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give 139 mg of crude material
  8. customPurification by flash chromatography
  9. customa 5 g silica gel cartridge, and mixtures of DCM and MeOH as eluent afforded impure product
  10. customRepurification by manual flash chromatography

Sources & evidence

ORD record
ord-1aa3307aa8d3482fb0ce7a6283c7b964
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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