Reaction #81380

Reaction equation

water

Methoxyethoxymethyl chloride

5-hydroxy-2-pyridinecarboxaldehyde

NaH

→

5-[(2-methoxyethoxy)methoxy]-2-pyridinecarboxaldehyde

Solvents

DMF

Conditions

Workup

1. 1
   Temperaturewhile cooling the mixture
2. 2
   Temperatureto maintain 20°-30° C
3. 3
   Otherwas evaporated
4. 4
   workup.ADDITIONwater was added to the residue
5. 5
   ExtractionThe mixture was extracted with EtOAc
6. 6
   DryingThe extracts were dried over Na2SO4
7. 7
   Filtrationfiltered
8. 8
   Otherevaporated to a residue
9. 9
   OtherThe residue was chromatographed on silica gel eluting with EtOAc-hexanes (35:65)

Procedure

Methoxyethoxymethyl chloride (MEM) (19 g, 153 mmol) was added to a solution of 5-hydroxy-2-pyridinecarboxaldehyde (18.4 g, 149 mmol) in 300 ml DMF. NaH (6.3 g of 60% oil dispersion, 158 mmol) were added in portions while cooling the mixture to maintain 20°-30° C. The mixture was stirred an additional 1 hour at 25° C. 5 ml water were added, most of the solvent was evaporated, and water was added to the residue. The mixture was extracted with EtOAc. The extracts were dried over Na2SO4, filtered, and evaporated to a residue. The residue was chromatographed on silica gel eluting with EtOAc-hexanes (35:65) to obtain 5-[(2-methoxyethoxy)methoxy]-2-pyridinecarboxaldehyde: C10H13NO4 (211.22); 1H-NMR (CDCl3) δ10.01 (s,1), 8.52 (d,1), 7.93 (d,1), 7.49 (m,1), 5.39 (s,2), 3.80 (m,2), 3.53 (m,2), 3.32 (s,3).

Source