Trifluoroacetic acid → ethyl {3-oxo-6-[(trifluoromethyl)oxy]-2,3-dihydro-4H-1,4-benzoxazin-4-yl}acetate

HRID 2354392Notes

Reaction equation

HRID 2354392 reaction equation
[F:1][C:2]([F:16])([F:15])[O:3][C:4]1[CH:5]=[CH:6][C:7]2[O:12][CH2:11][C:10](=[O:13])[NH:9][C:8]=2[CH:14]=1.[H-].[Na+].Br[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22].FC(F)(F)C(O)=O>O1CCCC1.CC#N.O>[O:13]=[C:10]1[N:9]([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:8]2[CH:14]=[C:4]([O:3][C:2]([F:1])([F:15])[F:16])[CH:5]=[CH:6][C:7]=2[O:12][CH2:11]1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 17778835HCID 17778835, compound

Product 1

HCID 57488861ethyl {3-oxo-6-[(trifluoromethyl)oxy]-2,3-dihydro-4H-1,4-benzoxazin-4-yl}acetateYield 73%

Reagents, catalysts & solvents 2

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

Procedure

A solution of 6-[(trifluoromethyl)oxy]-2H-1,4-benzoxazin-3(4H)-one (2.86 g, 12.3 mmol) dissolved in 13 mL of anhydrous tetrahydrofuran was added drop-wise to a mixture of sodium hydride (60% by weight in mineral oil, 0.54 g, 13.5 mmol) suspended in 26 mL of anhydrous tetrahydrofuran under argon. The mixture was allowed to stir at room temperature for 10 minutes and then ethyl bromoacetate (1.63 mL, 14.7 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=2.77 min and m/e 320 [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: 0% to 35% over 30 min; detection at 214 nm) to give ethyl {3-oxo-6-[(trifluoromethyl)oxy]-2,3-dihydro-4H-1,4-benzoxazin-4-yl}acetate (2.85 g, 8.9 mmol, 73%) as an orange oil. MS (ES) m/e 320 [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: 0% to 35% over 30 min

Sources & evidence

ORD record
ord-c23dcac4f3d84c3d90f4cf54e7b54fdc
Source dataset
uspto-grants-2010_07
Patent number
US07749998B2

Reaction notes

Loading…