Lithium hydride → 4-[(Benzyloxy)methyl]-6-bromo-2H-1,4-benzoxazin-3(4H)-one

HRID 1847075Notes

Reaction equation

HRID 1847075 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][C:8](=[O:11])[NH:7][C:6]=2[CH:12]=1.[H-].[Li+].Cl[CH2:16][O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C)C=O>[CH2:18]([O:17][CH2:16][N:7]1[C:6]2[CH:12]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=2[O:10][CH2:9][C:8]1=[O:11])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 62714Lithium hydride2×HCID 137983Benzyl chloromethyl ether2×HCID 162181426-Bromo-2H-1,4-benzoxazin-3(4H)-one

Product 1

HCID 867249994-[(Benzyloxy)methyl]-6-bromo-2H-1,4-benzoxazin-3(4H)-oneYield 91%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In N,N-dimethylformamide (4 ml) was dissolved 6-bromo-2H-1,4-benzoxazin-3(4H)-one (200 mg, 0.88 mmol). The solution was cooled in an ice bath, the reaction vessel was charged with nitrogen gas, lithium hydride (purity 90%, 11.7 mg, 1.32 mmol) was then added thereto and the mixture was stirred at room temperature for 10 minutes. Thereafter, benzyl chloromethyl ether (0.20 ml, 1.44 mmol) was added dropwise to the reaction solution at the same temperature and the mixture was stirred at the same temperature for 1.5 hours. Thereafter, lithium hydride (purity 90%, 2.3 mg, 0.26 mmol) and benzyl chloromethyl ether (0.04 ml, 0.29 mmol) were added while continuing stirring, whereby the reaction was quenched. The reaction solution was diluted with dichloromethane, washed with water (×4), dried over anhydrous magnesium sulfate and filtered, and the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate) to yield 278 mg (91%) of the title compound in the form of a white solid.

Workup

  1. temperatureThe solution was cooled in an ice bath
  2. additionwas then added
  3. stirringthe mixture was stirred at the same temperature for 1.5 hours
  4. stirringwhile continuing stirring
  5. customwhereby the reaction was quenched
  6. additionThe reaction solution was diluted with dichloromethane
  7. washwashed with water (×4)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customthe solvent was removed under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-c2116af14f3b4c3daff871c801e680b9
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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