Tert-butyl acetoacetate → tert-Butyl 6,6,6-trifluoro-3,5-dioxohexanoate

HRID 991756Notes

Reaction equation

HRID 991756 reaction equation
[H-].[Na+].[C:3]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].[Li]CCCC.[F:19][C:20]([F:30])([F:29])[C:21](OCC(F)(F)F)=[O:22]>C1COCC1>[C:10]([O:9][C:3](=[O:8])[CH2:4][C:5](=[O:6])[CH2:7][C:21](=[O:22])[C:20]([F:30])([F:29])[F:19])([CH3:13])([CH3:12])[CH3:11]

Participants

6

Reactant 4

HCID 15538Tert-butyl acetoacetateHCID 24758Sodium hydrideHCID 678882,2,2-Trifluoroethyl trifluoroacetateHCID 178418339Butyllithium

Product 1

HCID 45357312tert-Butyl 6,6,6-trifluoro-3,5-dioxohexanoateYield 38.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 60% NaH (2.2 g, 55 mmol; washed with hexanes) in THF (250 mL) at 0° C. was added dropwise tert-butyl acetoacetate (8.0 g, 50.6 mmol) over a period of 15 min. The mixture was stirred for 15 min. and a homogenous solution solution resulted. A solution of 2.5M n-BuLi in hexanes (20.5 mL, 51 mmol) was added dropwise. After stirring for 15 min., 2,2,2-trifluoroethyl trifluoroacetate (11 g, 56 mmol) was added and the mixture was stirred for 30 min., quenched with HOAc, diluted with H2O and extracted with EtOAc. The EtOAc extract was washed with H2O, dried (anhydrous MgSO4) and concentrated. Chromatography over silica gel and elution with hexanes:EtOAc (10:1), then hexanes:EtOAc (4:1) provided 5 g of title compound as a red-brown oil.

Workup

  1. customa homogenous solution solution resulted
  2. stirringAfter stirring for 15 min.
  3. stirringthe mixture was stirred for 30 min.
  4. customquenched with HOAc
  5. additiondiluted with H2O
  6. extractionextracted with EtOAc
  7. extractionThe EtOAc extract
  8. washwas washed with H2O
  9. dry with materialdried (anhydrous MgSO4)
  10. concentrationconcentrated
  11. washChromatography over silica gel and elution with hexanes:EtOAc (10:1)

Sources & evidence

ORD record
ord-7cfa468c255a4bada185dc0fec35a41d
Source dataset
uspto-grants-2002_10
Patent number
US06465509B2

Reaction notes

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