Methyl iodide → (RS)-6-[2-(2-Chloro-4-methoxy-phenyl)-propionyl]-4-methyl-4H-benzo[1,4]oxazin-3-one

HRID 2386750Notes

Reaction equation

HRID 2386750 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[CH2:10][C:11]([C:13]1[CH:14]=[CH:15][C:16]2[O:21][CH2:20][C:19](=[O:22])[N:18]([CH3:23])[C:17]=2[CH:24]=1)=[O:12].[H-].[Na+].[CH3:27]I>O1CCCC1>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[CH:10]([CH3:27])[C:11]([C:13]1[CH:14]=[CH:15][C:16]2[O:21][CH2:20][C:19](=[O:22])[N:18]([CH3:23])[C:17]=2[CH:24]=1)=[O:12]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 666972526-[2-(2-chloro-4-methoxy-phenyl)-acetyl]-4-methyl-4H-benzo[1,4]oxazin-3-one

Product 1

HCID 67546219(RS)-6-[2-(2-Chloro-4-methoxy-phenyl)-propionyl]-4-methyl-4H-benzo[1,4]oxazin-3-oneYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 6-[2-(2-chloro-4-methoxy-phenyl)-acetyl]-4-methyl-4H-benzo[1,4]oxazin-3-one (5.9 g, 17 mmol) in tetrahydrofuran (380 ml) was added sodium hydride (60% dispersion in mineral oil, 0.72 g, 17.9 mmol). The mixture was stirred at room temperature for 1.5 h and then placed in an ice bath. A solution of methyl iodide (2.54 g, 17.9 mmol) in tetrahydrofuran (15 ml) was added dropwise (5 min) The ice bath was removed and the mixture was stirred at 35° C. for 3.5 h. The reaction mixture was poured on ice-water and extracted twice with AcOEt. The organic phases were washed with water and brine, dried (MgSO4), filtered and concentrated. The product was purified by column chromatography (SiO2, heptane/EtOAc 2:1) to give the title compound (3.3 g) as a light yellow foam. MS (m/e)=360.2 [M+H+].

Workup

  1. customplaced in an ice bath
  2. customwas removed
  3. stirringthe mixture was stirred at 35° C. for 3.5 h
  4. additionThe reaction mixture was poured on ice-water
  5. extractionextracted twice with AcOEt
  6. washThe organic phases were washed with water and brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe product was purified by column chromatography (SiO2, heptane/EtOAc 2:1)

Sources & evidence

ORD record
ord-68cc4a37117443b9aa65942b13240ab1
Source dataset
uspto-grants-2012_09
Patent number
US08268820B2

Reaction notes

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