Reaction #44324

Reaction equation

sodium hydride

4-benzyloxybenzyl iodide

hexane

n-butyllithium

hydrochloric acid

acetylacetone

→

6-(4-benzyloxyphenyl)-2,4-hexanedione

Yield 63.0%

Solvents

THF

hexamethyl phosphoric triamide

THF

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   Otherto produce colorless precipitate
3. 3
   workup.DISSOLUTIONto dissolve the precipitate
4. 4
   workup.STIRRINGthe mixture was further stirred at 0° C. for 20 minutes
5. 5
   workup.STIRRINGAfter stirring the reaction mixture at room temperature for 1 hour
6. 6
   Temperatureit was cooled again to 0° C
7. 7
   WashAfter washing the organic layer with a saturated aqueous solution of sodium chloride
8. 8
   workup.DISTILLATIONthe solvent was distilled off
9. 9
   Othera rotary evaporator
10. 10
    Othera mixed solvent of dichloromethane/hexane of 1:1 (by volume ratio)) to separate a main product
11. 11
    OtherSeparation of this and
12. 12
    Concentrationconcentration to dryness under reduced pressure

Procedure

That is, 0.30 g (60% in oil) (7.5 mmol) of sodium hydride was weighed in a nitrogen atmosphere and 20 ml of THF was added thereto and the mixture was cooled to 0° C. in an ice bath. To the suspension was dripped a mixed solution of 0.75 g (7.5 mmol) of acetylacetone and 0.5 ml of hexamethyl phosphoric triamide to produce colorless precipitate. After stirring the mixture at 0° C. for 10 minutes, 4.6 ml (7.5 mmol) of a hexane solution (1.6 M) of n-butyllithium was dripped therein to dissolve the precipitate and the mixture was further stirred at 0° C. for 20 minutes. To the obtained pale yellow transparent solution was dripped a solution of 2.28 g (7.0 mmol) of 4-benzyloxybenzyl iodide in 10 ml of THF. After stirring the reaction mixture at room temperature for 1 hour, it was cooled again to 0° C. Then, dilute hydrochloric acid was added thereto to neutralize it. After washing the organic layer with a saturated aqueous solution of sodium chloride, the solvent was distilled off by using a rotary evaporator. The residue was passed through a silica gel column (eluent: a mixed solvent of dichloromethane/hexane of 1:1 (by volume ratio)) to separate a main product. Separation of this and concentration to dryness under reduced pressure afforded 1.31 g (4.4 mmol) of the objective 6-(4-benzyloxyphenyl)-2,4-hexanedione as pale yellow solid. Yield: 63%. Identification was performed by elementary analysis of C and H, and 1H-NMR.

Source