Reaction #67635

Reaction equation

5-bromo-2-chloro-3-methoxypyridine

3-bromo-5-methoxypyridine

sodium ethoxide ethanol

→

Compound 1016

5-bromo-2-ethoxy-3-methoxypyridine

Solvents

Water

Conditions

Workup

1. 1
   Otherthe reaction mixture microwave irradiated at 100° C. for 20 minutes
2. 2
   Otherthe ethanol evaporated under reduced pressure
3. 3
   ExtractionThe resulting aqueous solution was extracted with DCM and ether
4. 4
   Dryingby drying the combined extracts over MgSO4
5. 5
   FiltrationAfter filtration, removal of the volatiles under reduced pressure

Procedure

As shown in step 5-i of Scheme 5, 5-bromo-2-chloro-3-methoxypyridine (1.0 g, 4.5 mmol, prepared in the same manner as Compound 1003 in Example 2 starting with 3-bromo-5-methoxypyridine) was treated with a sodium ethoxide/ethanol solution (5.05 mL, 21% w/v, 13.5 mmol) and the reaction mixture microwave irradiated at 100° C. for 20 minutes. Water was added and the ethanol evaporated under reduced pressure. The resulting aqueous solution was extracted with DCM and ether, followed by drying the combined extracts over MgSO4. After filtration, removal of the volatiles under reduced pressure provided 5-bromo-2-ethoxy-3-methoxypyridine (Compound 1016), 0.72 g, 69% yield): ESMS (M+H) 232.32/234.23. As shown in step 5-ii of Scheme 5, Compound 1017 (ESMS (M+H) 218.32/220.23) was prepared in the same manner as Compound 1016, using sodium methoxide in methanol instead of sodium ethoxide in ethanol.

Source