Reaction #595327

Reaction equation

diethyl 3-oxopentanedioate

LDA

HCl

MeI

→

title compound

Yield 23.0%

Diethyl 2-methyl-3-oxopentanedioate

Yield 23.0%

Solvents

Et2O

Conditions

Workup

1. 1
   OtherThis compound was synthesized
2. 2
   OtherTo 20 mL of dry THF that had been purged with Ar(gas)
3. 3
   TemperatureThe reaction was maintained under Ar(gas) at −15° C.
4. 4
   workup.WAITthe stirring was continued overnight
5. 5
   workup.WAITAfter 18 hours
6. 6
   OtherThe organic layer was separated
7. 7
   Extractionthe aqueous layer was extracted twice with Et2O (15 mL×2)
8. 8
   Washwashed with brine
9. 9
   Dryingdried (MgSO4)
10. 10
    Concentrationconcentrated
11. 11
    Otherto give an yellow oil, which
12. 12
    Otherpurified (SiO2, Hexane:EtOAc=8:2 (v:v))

Procedure

This compound was synthesized according to U.S. Pat. No. 6,833,471. To 20 mL of dry THF that had been purged with Ar(gas) was added diethyl 3-oxopentanedioate (5 mL, 27.54 mmol) and the solution was cooled to −15° C. prior to the dropwise addition of LDA (2M) (15 mL, 30 mmol). The reaction was maintained under Ar(gas) at −15° C., and MeI (3 mL, 48.2 mmol) was added slowly. The reaction was allowed to reach room temperature gradually over 3 hours, and the stirring was continued overnight. After 18 hours, the reaction mixture was poured into 140 mL of a 1:1 mixture of 0.5 N HCl (aq) and Et2O. The organic layer was separated, and the aqueous layer was extracted twice with Et2O (15 mL×2). The organic layers were combined, washed with brine, dried (MgSO4) and concentrated to give an yellow oil, which was flash chromatography purified (SiO2, Hexane:EtOAc=8:2 (v:v)) to afford a colorless/light yellow oil as the title compound. (1.37 g, 23% yield). MW m/z: 215.3 (MW−1, low intensity). 1H NMR (CDCl3, 300 Hz) δ ppm 4.20 (q, 4H), 3.68 (q, 1H), 3.60 (dd, 2H), 1.37 (d, 3H), 1.26 (t, 6H).

Source