Ethyl bromodifluoroacetate → HCID 57577517, compound

HRID 1173639Notes

Reaction equation

HRID 1173639 reaction equation
C(O[C:6](=[O:19])[N:7]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=1)[C@@H:8]([CH3:11])[CH:9]=[O:10])(C)(C)C.Br[C:21]([F:28])([F:27])C(OCC)=O.S([O-])(O)(=O)=O.[K+].C(N(C(C)C)CC)(C)C>O1CCCC1.[Zn].O>[Cl:18][C:14]1[CH:13]=[C:12]([N:7]2[C@@H:8]([CH3:11])[C@H:9]([OH:10])[C:21]([F:28])([F:27])[C:6]2=[O:19])[CH:17]=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 69585Ethyl bromodifluoroacetateHCID 81531DiisopropylethylamineHCID 516920Potassium bisulfateHCID 59556963HCID 59556963, compound

Product 1

HCID 57577517HCID 57577517, compoundYield 21%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

tert-Butyl(3-chlorophenyl)[(1S)-1-methyl-2-oxoethyl]carbamate (19.5 g) and ethyl bromodifluoroacetate (41.3 g) were dissolved in tetrahydrofuran (110 mL), and to a suspension of a zinc powder (13.6 g) in tetrahydrofuran (25 mL) was added dropwise the solution at room temperature. After heating under reflux for 1 hr, the mixture was cooled to room temperature, 1 mol/L aqueous potassium hydrogen sulfate solution (300 mL) was added, and the mixture was extracted with ethyl acetate. The extracted organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=0→10%), the obtained oil was dissolved in 4 mol/L hydrogen chloride/ethyl acetate solution (100 mL), and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated under reduced pressure, tetrahydrofuran (275 mL) and diisopropylethylamine (21.3 mL, 119 mmol) were added, and the mixture was heated under reflux for 12 hr. The reaction solution was cooled to room temperature, water (200 mL) was added, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=10→40%) to give the title compound as a yellow oil (yield: 3.76 g, 21%).

Workup

  1. additionwas added dropwise the solution at room temperature
  2. temperatureAfter heating
  3. temperatureunder reflux for 1 hr
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extracted organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=0→10%)
  9. dissolutionthe obtained oil was dissolved in 4 mol/L hydrogen chloride/ethyl acetate solution (100 mL)
  10. additionwere added
  11. temperaturethe mixture was heated
  12. temperatureunder reflux for 12 hr
  13. temperatureThe reaction solution was cooled to room temperature
  14. extractionthe mixture was extracted with ethyl acetate
  15. washThe obtained organic layer was washed with saturated brine
  16. dry with materialdried over anhydrous magnesium sulfate
  17. concentrationconcentrated under reduced pressure
  18. customThe residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=10→40%)

Sources & evidence

ORD record
ord-fb37e12522924eb899e013bf4d48b5b1
Source dataset
uspto-grants-2010_11
Patent number
US07834051B2

Reaction notes

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