tert-Butanol → HCID 2758966, compound

HRID 241005Notes

Reaction equation

HRID 241005 reaction equation
CC(C)([O-])C.[K+].[C:7]([O:13][CH3:14])(=[O:12])[CH2:8][C:9]([CH3:11])=[O:10].C(O)(C)(C)C.[F:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Br)=[CH:23][CH:22]=1>O1CCCC1>[F:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][CH:8]([C:9](=[O:10])[CH3:11])[C:7]([O:13][CH3:14])=[O:12])=[CH:23][CH:22]=1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 7757Methyl acetoacetateHCID 680214-Fluorobenzyl bromideHCID 23665647Potassium tert-butoxide

Product 1

HCID 2758966HCID 2758966, compoundYield 75.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of potassium tert-butoxide (10.6 g, 95.0 mmol) in tetrahydrofuran (100 mL) were added methyl acetoacetate (10.0 g, 86.0 mmol) and tert-butanol (0.83 mL, 8.6 mmol) at room temperature. The resulting solution was stirred for 1 h, and then 4-fluorobenzylbromide (11.2 mL, 90 mmol) was added. The reaction mixture was stirred at room temperature for 18 h, and then partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate (3×), the combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. Column chromatography of the residue on silica (5-20% ethyl acetate in hexanes) gave methyl 2-(4-fluorobenzyl)-3-oxobutanoate (14.5 g, 75% yield) as a colorless oil which was used in the next step without further purification.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 18 h
  2. custompartitioned between water and ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×)
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-25e9391a7e524fa282c44782ab6843fd
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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