Pinacolone → N-(2-adamantyl)-4,4-dimethyl-3-oxo-pentanamide

Temperature

-78 °C

A 1M solution of solution of lithium bis(trimethylsilyl)amide in THF (22.84 ml, 22.84 mmol) was added to THF (25 mL) and cooled under nitrogen to −78° C. A solution of 3,3-dimethyl-2-butanone (2.287 g, 22.84 mmol) in THF (25 mL) was added drop wise over a period of 5 minutes. The resulting solution was stirred at −78° C. under nitrogen for minutes. A solution of 2-isocyanatoadamantane (prepared from 2-adamantylamine hydrochloride by the method of R. Reck & C. Jochims Chem. Ber. 115 (1982) p 864) (3.68 g, 20.76 mmol) in THF (20 mL) was added over a period of 5 minutes. The resulting solution was stirred at −78° C. for 1 hour and then allowed to warm to 20° C. over 1 h. The reaction mixture was poured into saturated NH4Cl (150 mL) and extracted with EtOAc (2×100 mL), the organic layer was washed with water (50 mL) and brine (50 mL) dried over MgSO4, filtered and evaporated to afford a yellow oil. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford N-(2-adamantyl)-4,4-dimethyl-3-oxo-pentanamide (4.64 g, 81%) as a white solid.

1. stirringThe resulting solution was stirred at −78° C. for 1 hour
2. temperatureto warm to 20° C. over 1 h
3. extractionextracted with EtOAc (2×100 mL)
4. washthe organic layer was washed with water (50 mL) and brine (50 mL)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. customevaporated
8. customto afford a yellow oil
9. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane
10. customPure fractions were evaporated to dryness

ORD record

ord-7a21be87ff0045639368a64393dbdd1f

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08344016B2