Trifluoroacetic acid → HCID 57488853, compound

HRID 2354367Notes

Reaction equation

HRID 2354367 reaction equation
[CH3:1][O:2][C:3]1[CH:13]=[CH:12][C:6]2[NH:7][C:8](=[O:11])[CH2:9][O:10][C:5]=2[CH:4]=1.[H-].[Na+].Br[CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19].FC(F)(F)C(O)=O>C1COCC1.CC#N.O>[CH3:1][O:2][C:3]1[CH:13]=[CH:12][C:6]2[N:7]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:8](=[O:11])[CH2:9][O:10][C:5]=2[CH:4]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 116007707-Methoxy-2H-1,4-benzoxazin-3(4H)-one

Product 1

HCID 57488853HCID 57488853, compoundYield 64.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

A solution of 7-(methyloxy)-2H-1,4-benzoxazin-3(4H)-one (1.42 g, 7.9 mmol) dissolved in 5 mL of anhydrous THF was added to a suspension of sodium hydride (0.349 g of a 60% dispersion in mineral oil, 8.7 mmol) in 10 mL of anhydrous THF at room temperature and stirred for 10 minutes. Then, ethyl bromoacetate (1.06 mL, 9.52 mmol) was added and stirred at room temperature for two hours. HPLC (Eclipse XDB-C18, 4.6×250 mm, 5 micron, 1-99% CH3CN/H2O with 0.1% trifluoroacetic acid) showed that all of the starting material (Rt=4.4 min) was gone and that a new peak (Rt=6.5 min) had formed. The reaction was quenched with 5 mL of 4.0M HCl in dioxane. The solvent was removed by rotary evaporation and the residue was adsorbed onto approximately 10 g of silica gel and purified by column chromatography (120 g silica gel 40 um, gradient elution from 100% dichloromethane to 10% methanol/90% dichloromethane over 40 minutes) to give ethyl [7-(methyloxy)-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl]acetate (1.35 g, 5.1 mmol, 64%) as a white crystalline solid. MS (ES) m/e 266 [M+H]+.

Workup

  1. stirringstirred at room temperature for two hours
  2. customhad formed
  3. customThe reaction was quenched with 5 mL of 4.0M HCl in dioxane
  4. customThe solvent was removed by rotary evaporation
  5. custompurified by column chromatography (120 g silica gel 40 um, gradient elution from 100% dichloromethane to 10% methanol/90% dichloromethane over 40 minutes)

Sources & evidence

ORD record
ord-12fc6795f41041e1a65bff5d832fe575
Source dataset
uspto-grants-2010_07
Patent number
US07749998B2

Reaction notes

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