Ethyl isobutyrate → Ethyl 5-bromo-2,2-dimethylpentanoate

Temperature

-78 °C

To a 0° C. solution of diisopropylamine (14.35 mL, 0.102 mol) in 70 mL of THF was added n-BuLi (68 mL, 0.102 mol). The mixture was stirred at 0˜5° C. for 30 min. After the mixture was cooled to −78° C., ethyl isobutyrate (13.7 mL, 0.102 mol, 1 eq.) was added drop wise and stirring was maintained at −78° C. for 1 h. 1,3-Dibromopropane (1.01 equiv, 10.5 mL) was added drop wise at −78° C. and stirring was maintained at −78° C. for 1 h. Reaction was then warmed up to 23° C. over 2 hrs. Reaction mixture was added to an aqueous NH4Cl solution and extracted with EtOAc. The organic layer was washed with 1N HCl and brine, dried over MgSO4, filtered and concentrated down to give 23 g of crude product. The residue was purified by silica gel chromatography (5% to 30% EtOAc in hexanes) to provide 17.4 g (73% yield) of ethyl 5-bromo-2,2-dimethylpentanoate 90.

1. stirringstirring
2. temperaturewas maintained at −78° C. for 1 h
3. stirringstirring
4. temperaturewas maintained at −78° C. for 1 h
5. customReaction
6. temperaturewas then warmed up to 23° C. over 2 hrs
7. customReaction mixture
8. extractionextracted with EtOAc
9. washThe organic layer was washed with 1N HCl and brine
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated down
13. customto give 23 g of crude product
14. customThe residue was purified by silica gel chromatography (5% to 30% EtOAc in hexanes)

ORD record

ord-6d9188bda33147529b56051450095755

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08859776B2