Chlorotrimethylsilane → 5-Bromo-3,3-dimethyltetrahydro-4H-pyran-4-one

Temperature

-78 °C

A solution of lithium diisopropylamine (2.0 M in heptanes/THF/ethylbenzene) (2.5 ml, 5.1 mmol) diluted with THF (10 mL) under argon was cooled to −78° C. Chlorotrimethylsilane (2.5 mL, 19.5 mmol) was added followed by 3,3-dimethyldihydro-2H-pyran-4(3H)-one (compound 449.1, 500 mg, 3.9 mmol) in THF (5 mL) and triethylamine (8.0 mL, 57 mmol). The resulting mixture was stirred at −78° C. for 5 minutes and then quenched with saturated NaHCO3 (20 mL). The mixture was extracted with ether (30 mL) and the organics was washed with 1M citric acid (50 mL), dried (K2CO3), filtered and concentrated in vacuo. The residue was dissolved in THF (5 mL) and cooled to 0° C. N-Bromosuccinimide (694 mg, 3.9 mmol) was added and the resulting mixture was stirred at room temperature for 2 hrs and then quenched with saturated NaHCO3 (10 mL). The mixture was extracted with ether (2×20 mL) and the organics was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (8% ethyl acetate in hexane) to yield the title compound as an oil (150 mg, 18%).

1. customquenched with saturated NaHCO3 (20 mL)
2. extractionThe mixture was extracted with ether (30 mL)
3. washthe organics was washed with 1M citric acid (50 mL)
4. dry with materialdried (K2CO3)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. dissolutionThe residue was dissolved in THF (5 mL)
8. temperaturecooled to 0° C
9. stirringthe resulting mixture was stirred at room temperature for 2 hrs
10. customquenched with saturated NaHCO3 (10 mL)
11. extractionThe mixture was extracted with ether (2×20 mL)
12. washthe organics was washed with brine
13. dry with materialdried (MgSO4)
14. filtrationfiltered
15. concentrationconcentrated in vacuo
16. customThe residue was purified by silica gel chromatography (8% ethyl acetate in hexane)

ORD record

ord-1c630cf596ad4b1db14796327831d19e

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08871790B2