Ethyl isobutyrate → Ethyl 2,2-dimethylpent-4-ynoate

Temperature

0 °C

A solution of n-BuLi (199 mL, 498 mmol) as 2.5M in hexane was added slowly to a stirred solution of DIPA (74.3 mL, 521 mmol) in anhydrous THF (500 mL), at −75° C. and under nitrogen. The solution was stirred for 20 minutes, and a solution of ethyl isobutyrate (64 mL, 474 mmol) in THF (100 mL) was added dropwise to the solution over 1.5 hours. The solution was warmed to 0° C. and recooled to −75° C., then a solution of propargyl bromide (53.6 mL, 498 mmol) as 80% in PhMe was added dropwise. The reaction solution was slowly warmed to 22° C. and stirred for 20 hours, then quenched with water (150 mL). The water layer was extracted with ether (2×200 mL). The combined organic layer was washed with water (150 mL), brine (100 mL), dried over Na2SO4, filtered and concentrated. The residue was chromatographed on silica gel 60 eluting with 0 to 25% EtOAc in hexane, to give the title product. 1H NMR (500 MHz, CDCl3) δ 4.12 (q, J=7.1 Hz, 2H); 2.41 (s, 2H); 1.98 (s, 1H); 1.25 (s, 6H); 1.23 (t, J=7.1 Hz, 3H) ppm.

1. customrecooled to −75° C.
2. temperatureThe reaction solution was slowly warmed to 22° C.
3. stirringstirred for 20 hours
4. customquenched with water (150 mL)
5. extractionThe water layer was extracted with ether (2×200 mL)
6. washThe combined organic layer was washed with water (150 mL), brine (100 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was chromatographed on silica gel 60 eluting with 0 to 25% EtOAc in hexane

ORD record

ord-630c51b47121430c9ad76f5813f009db

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08309540B2