Methyl iodide → 5-bromo-1-methyl-3-morpholinopyridin-2(1H)-one

HRID 594051Notes

Reaction equation

HRID 594051 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[C:5](=[O:8])[NH:6][CH:7]=1.[C:15](=O)([O-])[O-].[K+].[K+].IC>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[C:5](=[O:8])[N:6]([CH3:15])[CH:7]=1.[Br:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[C:5]([O:8][CH3:15])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 904098535-Bromo-3-morpholinopyridin-2-ol

Product 2

HCID 904089385-bromo-1-methyl-3-morpholinopyridin-2(1H)-oneHCID 904090924-(5-Bromo-2-methoxypyridin-3-yl)morpholine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-bromo-3-morpholinopyridin-2(1H)-one (1.0 equiv.) in DMF (0.2 M) was added potassium carbonate (2.0 equiv.), followed by iodomethane (1.0 equiv.). The solution was stirred at room temperature for 3 hours. The solution was partitioned between water and ethyl acetate, the organic phase was washed with brine, dried with sodium sulfate, filtered and concentrated. The crude material was a mixture of N-methylated and O-methylated products (90:10). The material could be used for the next step without further purification as a mixture of isomers or it could be purified via silica gel column chromatography eluting with 0-100% ethyl acetate in heptanes to afford 5-bromo-1-methyl-3-morpholinopyridin-2(1H)-one in 71% yield LCMS (m/z) (M+H)=273/275, Rt=0.55 min and 4-(5-bromo-2-methoxypyridin-3-yl)morpholine in 10% yield. LCMS (m/z) (M+H)=273/275, Rt=0.82 min.

Workup

  1. customThe solution was partitioned between water and ethyl acetate
  2. washthe organic phase was washed with brine
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additiona mixture of N-methylated and O-methylated products (90:10)
  7. customThe material could be used for the next step without further purification as a mixture of isomers or it
  8. customcould be purified via silica gel column chromatography
  9. washeluting with 0-100% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-50a8aefd49114e2383c9ca1a194b5160
Source dataset
uspto-grants-2016_01
Patent number
US09242969B2

Reaction notes

Loading…