Methyl chloroacetate → 6-Methyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

HRID 723515Notes

Reaction equation

HRID 723515 reaction equation
[NH2:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[C:4]([CH3:9])[N:3]=1.CC1N=C([N+]([O-])=O)[C:14]([OH:20])=[CH:13]C=1.[H-].[Na+].ClCC(OC)=O>CS(C)=O>[CH3:9][C:4]1[CH:5]=[CH:6][C:7]2[O:8][CH2:13][C:14](=[O:20])[NH:1][C:2]=2[N:3]=1

Participants

6

Reactant 4

HCID 7295Methyl chloroacetateHCID 24758Sodium hydrideHCID 848016-Methyl-2-nitropyridin-3-olHCID 885002-Amino-6-methylpyridin-3-ol

Product 1

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

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2-amino-6-methyl-pyridin-3-ol (5.7 g, 46 mmol) (prepared by reduction of 6-methyl-2-nitro-pyridin-3-ol according to the procedure of J. Kaminski et al, [J. Med. Chem, 30 (11), 2031 (1987)1 in dimethylsulphoxide (60 ml) was treated with sodium hydride (44 mmol) under argon. After 0.25 hours methyl chloroacetate (4 mL, 5 g, 46 mmol) was added and the mixture heated at 100° C. for 3.5 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride solution (10 mL), then partitioned between dichloromethane and water. The organic extracts were dried and evaporated and the residue was chromatographed eluting with 0-20% ethyl acetate in dichloromethane affording the product as a white crystalline solid (4.7 g, 62%).

Workup

  1. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution (10 mL)
  2. custompartitioned between dichloromethane and water
  3. customThe organic extracts were dried
  4. customevaporated
  5. customthe residue was chromatographed
  6. washeluting with 0-20% ethyl acetate in dichloromethane affording the product as a white crystalline solid (4.7 g, 62%)

Sources & evidence

ORD record
ord-28e10002f9cd46f6840567a4d1b7384c
Source dataset
uspto-grants-2006_11
Patent number
US07141564B2

Reaction notes

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