Methyl iodide → 6-Methylspiro[2.5]octan-5-one

Temperature

-75 °C

Spiro[2.5]octan-5-one (2.4 g, 19.32 mmol) was dissolved in THF (100 mL) and cooled to −75° C. At that temperature LHMDS 1M in THF (24 mL, 24 mmol) was added dropwise over 15 minutes. The resulting pale yellow solution was stirred 1 hour at −75° C. Iodomethane (1.3 mL, 21.26 mmol) was added and stirring was continued at −75° C. for another hour before letting the mixture warm up to RT. The reaction was quenched by addition of saturated aqueous NH4Cl. The layers were separated and the aqueous layer was extracted with Et2O. The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The remaining yellow oil was purified by SiO2 chromatography (330 g SiO2, hexanes/EtOAc 0 to 3% EtOAc) to give 0.93 g of racemic 6-methyl-spiro[2.5]octan-5-one as a colorless liquid (35% yield).

1. stirringstirring
2. waitwas continued at −75° C. for another hour
3. temperaturewarm up to RT
4. customThe reaction was quenched by addition of saturated aqueous NH4Cl
5. customThe layers were separated
6. extractionthe aqueous layer was extracted with Et2O
7. washThe combined organic layers were washed with brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. customevaporated
11. customThe remaining yellow oil was purified by SiO2 chromatography (330 g SiO2, hexanes/EtOAc 0 to 3% EtOAc)

ORD record

ord-d3153a246e1549daaa3ed3d111627def

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08012974B2