3-Bromo-5-methoxypyridine → 5-Bromo-2-ethoxy-3-methoxypyridine

HRID 2387769Notes

Reaction equation

HRID 2387769 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([O:8][CH3:9])[CH:7]=1.[O-:10][CH2:11][CH3:12].[Na+].C(O)C>O>[Br:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([O:10][CH2:11][CH3:12])=[N:4][CH:3]=1

Participants

4

Reactant 2

HCID 8171633-Bromo-5-methoxypyridineHCID 23706232Ethanol sodium ethoxide

Product 1

HCID 666174235-Bromo-2-ethoxy-3-methoxypyridine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

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.

Workup

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

Sources & evidence

ORD record
ord-e26c5a00914143808cc9ffbdeb502cc8
Source dataset
uspto-grants-2012_09
Patent number
US08268999B2

Reaction notes

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