Trifluoroacetic acid → HCID 57457149, compound

HRID 2114382Notes

Reaction equation

HRID 2114382 reaction equation
[O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:10]=[CH:11][C:5]=2[O:4][CH2:3]1.[H-].[Na+].[C:19]([O:23][C:24](=[O:27])[CH2:25]Br)([CH3:22])([CH3:21])[CH3:20].FC(F)(F)C(O)=O>O1CCCC1.CC#N.O>[CH3:20][C:19]([O:23][C:24](=[O:27])[CH2:25][N:7]1[C:6]2[CH:8]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:10]=[CH:11][C:5]=2[O:4][CH2:3][C:2]1=[O:1])([CH3:22])[CH3:21]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 1445529Ethyl 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate2×

Product 1

HCID 57457149HCID 57457149, compoundYield 96%

Reagents, catalysts & solvents 2

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

Procedure

Several smaller batches of ethyl 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate were combined. A solution of ethyl 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate (4.1 g, 19.0 mmol) dissolved in 30 mL of anhydrous tetrahydrofuran was added drop-wise to a mixture of sodium hydride (60% by weight in mineral oil, 0.8 g, 20 mmol) suspended in 60 mL of anhydrous tetrahydrofuran under argon. The mixture was allowed to stir at room temperature for 10 minutes before t-butyl-2-bromoacetate (3.4 mL, 23 mmol) was added to the mixture and stirred vigorously for 2 hours. HPLC (Eclipse XDB-C18, 4.6×250 mm, 5 micron, 1-99% CH3CN/H2O with 0.1% trifluoroacetic acid) chromatogram indicated that all of the starting material (Rt=5.5 min) was consumed and only a single new product had formed (Rt=7.7 min). The reaction was quenched by adding 8 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 to give ethyl 4-{2-[(1,1-dimethylethyl)oxy]-2-oxoethyl}-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate (6.14 g, 18.0 mmol, 96%). MS (ES) m/e 280 [M−t-butyl C4H9]+.

Workup

  1. additionwas added drop-wise
  2. additionwas added to the mixture
  3. customwas consumed
  4. customonly a single new product had formed (Rt=7.7 min)
  5. customThe reaction was quenched
  6. additionby adding 8 mL of a 4 M solution of hydrochloric acid in dioxane
  7. stirringto stir for one hour
  8. customall of the volatiles were removed by rotary evaporation

Sources & evidence

ORD record
ord-841b4ce980a2410998fb0b46e57794c4
Source dataset
uspto-grants-2008_10
Patent number
US07432258B2

Reaction notes

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