Tert-butyl acetoacetate → 1-Tert-butyl 7-ethyl 2-acetylheptanedioate

HRID 2250549Notes

Reaction equation

HRID 2250549 reaction equation
[O:1]=[C:2]([CH3:11])[CH2:3][C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].[H-].[Na+].I[CH2:15][CH2:16][CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20]>O1CCCC1>[C:2]([CH:3]([CH2:15][CH2:16][CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])(=[O:1])[CH3:11]

Participants

5

Reactant 3

HCID 15538Tert-butyl acetoacetateHCID 24758Sodium hydrideHCID 4169827Ethyl 5-iodopentanoate

Product 1

HCID 574812961-Tert-butyl 7-ethyl 2-acetylheptanedioateYield 75.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 3-oxobutanoate (20.0 g) in tetrahydrofuran (200 mL) was added 60% sodium hydride in oil (556 g) portionwise over 20 minutes in an ice-water bath under N2. After 40 minutes, to the mixture was added ethyl 5-iodopentanoate (35.6 g) at the temperature. After 15 minutes, the mixture was stirred at ambient temperature. After 1 hour, the reaction mixture was heated at 50° C. for 24 hours. The cooled mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by flash silica gel chromatography (silica gel, 1 L) eluting with hexane-ethyl acetate=50-1, 20-1, 10-1, and 8-1 to give 1-tert-butyl 7-ethyl 2-acetylheptanedioate (27.3 g, 75.4%) as colorless oil.

Workup

  1. waitAfter 15 minutes
  2. waitAfter 1 hour
  3. temperaturethe reaction mixture was heated at 50° C. for 24 hours
  4. customThe cooled mixture was partitioned between ethyl acetate and water
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. washThe combined organic layer was washed with water and brine
  7. dry with materialdried over magnesium sulfate
  8. customevaporated in vacuo
  9. customThe residue was purified by flash silica gel chromatography (silica gel, 1 L)
  10. washeluting with hexane-ethyl acetate=50-1, 20-1, 10-1, and 8-1

Sources & evidence

ORD record
ord-c132a8af699f48209157f0edfd8c09aa
Source dataset
uspto-grants-2008_01
Patent number
US07317009B2

Reaction notes

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