Methyl acetoacetate → 6-(2-Cyclohex-1-enyl-ethyl)-6-cyclopentyl-dihydro-pyran-2,4-dione

Methyl acetoacetate (0.66 g, 5.7 mmol) was added to a cooled 0° C. suspension of NaH (0.23 g, 5.7 mmol, 60% dispersion in mineral oil) in THF (10 ml). After 30 min n-BuLi (2.3 mL, 5.7 mmol, 2.5M in hexanes) was added. The resulting dianion was stirred for an additional 30 min and then treated with a solution 3-Cyclohex-1-enyl-1-cyclopentyl-propan-1-one (0.39 g, 1.9 mmol, Step 4 below) in THF (3 ml). After stirring for 4 h at 0° C., the reaction mixture was quenched with 1N HCl and extracted with EtOAc. The organic layers were washed with brine, dried over Na2SO4 and concentrated to an orange oil that was used without further purification. The oil was dissolved in methanol (8 mL), treated with potassium carbonate (0.79 g, 5.7 mmol), and refluxed under N2 for 90 min. The reaction mixture was partitioned between 1N HCl and EtOAc. The organic layers were washed with brine, dried over Na2SO4 and concentrated to an orange oil that was purified by silica gel chromatography (0% to 20% EtOAc in hexanes). to give the title compound as a white solid. (0.22 g, 40% yield).

1. stirringAfter stirring for 4 h at 0° C.
2. customthe reaction mixture was quenched with 1N HCl
3. extractionextracted with EtOAc
4. washThe organic layers were washed with brine
5. dry with materialdried over Na2SO4
6. concentrationconcentrated to an orange oil that
7. customwas used without further purification
8. dissolutionThe oil was dissolved in methanol (8 mL)
9. temperaturerefluxed under N2 for 90 min
10. customThe reaction mixture was partitioned between 1N HCl and EtOAc
11. washThe organic layers were washed with brine
12. dry with materialdried over Na2SO4
13. concentrationconcentrated to an orange oil that
14. customwas purified by silica gel chromatography (0% to 20% EtOAc in hexanes)

ORD record

ord-5d117f32bab44e2d8ff523960def5807

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07148226B2