Potassium Carbonate → (7-nitro-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-3-yl)methanol

HRID 2102974Notes

Reaction equation

HRID 2102974 reaction equation
[NH2:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:19][CH:20]1[O:22][CH2:21]1>CCOC(C)=O>[N+:9]([C:5]1[CH:4]=[N:3][C:2]2[NH:1][CH:20]([CH2:21][OH:22])[CH2:19][O:8][C:7]=2[CH:6]=1)([O-:11])=[O:10]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 18430EpibromohydrinHCID 53734252-Amino-5-nitropyridin-3-ol

Product 1

HCID 68703685(7-nitro-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-3-yl)methanolYield 49%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Into a 75 mL sealed tube were combined 2-amino-3-hydroxy-5-nitropyridine (0.138 g, 0.000890 mol), N,N-dimethylfonnamide (4.1 mL) and potassium carbonate (0.39 g, 0.0028 mol). The mixture was allowed to stir at room temperature for 10 minutes then 1-bromo-2,3-epoxypropane (0.12 g, 0.00089 mol) was added in one portion. The flask was sealed, then heated to 110° C. and stirred overnight. After allowing to cool, the mixture was concentrated under vacuum to give a crude solid which was dissolved in EtOAc (75 mL), washed with water and brine, then dried (Na2SO4), filtered and concentrated under vacuum to leave a crude residue. The residue was purified by column chromatography on silica gel using MeOH/CH2Cl2 (0-10% gradient) as eluent to give a solid (0.092 g, 46%). LC-MS 1.92 min. M/Z=212.0 (M+1). 1H NMR (d6-DMSO) δ 8.8 (d, 1 H), 7.8 (d, 1 H), 5.1 (t, 1H),4.2 (m, 1 H), 4.0 (m, 1H), 3.62 (m, 1H), 3.45 (m, 1H), 3.21 (m, 1H).

Workup

  1. customInto a 75 mL sealed tube
  2. customThe flask was sealed
  3. temperatureheated to 110° C.
  4. stirringstirred overnight
  5. temperatureto cool
  6. concentrationthe mixture was concentrated under vacuum
  7. customto give a crude solid which
  8. washwashed with water and brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated under vacuum
  12. customto leave a crude residue
  13. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-7dad398bd04d4836a5bfa8fe10a41098
Source dataset
uspto-grants-2009_08
Patent number
US07576099B2

Reaction notes

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