Aluminium lithium hydride → 6-methyl-2H,3H,4H-pyrido[3,2-b][1,4]oxazine

HRID 24057Notes

Reaction equation

HRID 24057 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][C:8]1[CH:9]=[CH:10][C:11]2[O:12][CH2:13][C:14](=O)[NH:15][C:16]=2[N:17]=1>C1COCC1>[CH3:7][C:8]1[CH:9]=[CH:10][C:11]2[O:12][CH2:13][CH2:14][NH:15][C:16]=2[N:17]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 218737086-Methyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

Product 1

HCID 223194636-methyl-2H,3H,4H-pyrido[3,2-b][1,4]oxazineYield 99.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A flask was charged with lithium aluminum hydride (607 mg, 16.0 mmol) was placed in an ice-water bath under an argon atmosphere. THF (13 mL) was added slowly. To this suspension was added slowly a solution of 6-methyl-4H-pyrido[3,2-b][1,4]oxazin-3-one (1.05 g, 6.40 mmol) in THF (13 mL). After the addition was completed, additional THF (9 mL) was added, and the reaction was stirred in the ice-water bath for 30 minutes. Ice-water bath was removed, the mixture was stirred at ambient temperature for 3 h. The mixture was cooled with an ice-water bath, and H2O (0.86 mL) was added slowly, followed by cooled aqueous NaOH solution (0.64 mL, 10%). The ice-water bath was removed, additional H2O (1.8 mL) was added. After stirring for 30 minutes, Celite and Na2SO4 were added. The mixture was filtered through Celite, and the Celite was washed with EtOAc. The filtrate and the washing were combined, dried over Na2SO4, and concentrated to give the title compound (0.96 g, quantitative yield) as a while solid. 1H NMR (CDCl3) δ 6.85 (d, 1H, J=8.0 Hz), 6.35 (d, 1H, J=8.0 Hz), 6.08 (bs, 1H), 4.19-4.16 (m, 2H), 3.54-3.52 (m, 2H), 2.31 (s, 3H).

Workup

  1. customwas placed in an ice-water bath under an argon atmosphere
  2. additionAfter the addition
  3. customIce-water bath was removed
  4. temperatureThe mixture was cooled with an ice-water bath
  5. additionH2O (0.86 mL) was added slowly
  6. temperatureby cooled aqueous NaOH solution (0.64 mL, 10%)
  7. customThe ice-water bath was removed
  8. additionadditional H2O (1.8 mL) was added
  9. stirringAfter stirring for 30 minutes
  10. additionCelite and Na2SO4 were added
  11. filtrationThe mixture was filtered through Celite
  12. washthe Celite was washed with EtOAc
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-23c721f5ed1a44b4b33287c867651d44
Source dataset
uspto-grants-2005_02
Patent number
US06855722B2

Reaction notes

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