Trifluoroacetic acid → HCID 57488859, compound

HRID 2114391Notes

Reaction equation

HRID 2114391 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH2:10][C:9](=[O:12])[NH:8][C:7]=2[CH:13]=1.[H-].[Na+].Br[CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19].FC(F)(F)C(O)=O>O1CCCC1.CC#N.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH2:10][C:9](=[O:12])[N:8]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:7]=2[CH:13]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 132049526-methoxy-3,4-dihydro-2H-1,4-benzoxazin-3-one

Product 1

HCID 57488859HCID 57488859, compoundYield 60%

Reagents, catalysts & solvents 2

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

Procedure

A solution of 6-(methyloxy)-2H-1,4-benzoxazin-3(4H)-one (2.08 g, 11.6 mmol) dissolved in 12.5 mL of anhydrous tetrahydrofuran was added drop-wise to a mixture of sodium hydride (60% by weight in mineral oil, 0.52 g, 12.8 mmol) suspended in 25 mL of anhydrous tetrahydrofuran under argon. The mixture was allowed to stir at room temperature for 10 minutes and then ethyl bromoacetate (1.54 mL, 13.9 mmol) was added to the mixture and stirred vigorously for 1.5 hours before it was determined to be complete by LCMS (two Aquasil C18, 20×1 mm columns were run in sequence, 4 minutes at 0.1 mL/min, 1-99% CH3CN/H2O with 0.018% trifluoroacetic acid, ES) Rt=1.5 min and m/e 265 [M+1]+. The reaction was quenched by adding 5 mL of a 4 M solution of hydrochloric acid in dioxane. After allowing the mixture to stir for one hour, all of the volatiles were removed by rotary evaporation, and the crude residue was purified by silica gel chromatography (120 g Redisep column, silica, 40 um, 60 Å, 50 mL/min, A: methylene chloride, B: methanol, B: 10% for 5 min, 80% for 30 min; detection at 214 nm) to give ethyl [6-(methyloxy)-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl]acetate (1.82 g, 6.9 mmol, 60%). MS (ES) m/e 265 [M+1]+.

Workup

  1. additionwas added drop-wise
  2. stirringstirred vigorously for 1.5 hours before it
  3. customThe reaction was quenched
  4. additionby adding 5 mL of a 4 M solution of hydrochloric acid in dioxane
  5. stirringto stir for one hour
  6. customall of the volatiles were removed by rotary evaporation
  7. customthe crude residue was purified by silica gel chromatography (120 g Redisep column, silica, 40 um, 60 Å, 50 mL/min
  8. waitA: methylene chloride, B: methanol, B: 10% for 5 min
  9. wait80% for 30 min

Sources & evidence

ORD record
ord-efb1b0ff0ae84c7892afe2d8aeb7e1c0
Source dataset
uspto-grants-2008_10
Patent number
US07432258B2

Reaction notes

Loading…