2,2,6,6-Tetramethylpiperidine → HCID 178418821, compound

A solution of n-butyllithium (17.6 ml, 44 mmol, 2.5M in hexane) was added to a solution of 2,2,6,6-tetramethylpiperidine (6.8 g, 48 mmol) in 50 ml THF at 0° C. to form LTMP. In a separate flask, a solution of the product of step 2 (4.4 g, 20 mmol) and dibromomethane (7.6 g,44 mmol) in 40 ml THF was cooled to −70° C. After 30 min, LTMP solution was cooled to −70° C., and added to above solution via a cannula at −65° C. over 30 min. After 10 min, a solution of lithium bis(trimethyl)silyl amide solution (40 ml, 40 mmol, 1M in THF) was added over 15 min at −70° C. The resulting mixture was allowed to warm to −20° C. and then cooled back to −70° C. A solution of s-butyllithium solution (61.6 ml, 80 mmol, 1.3 M in cyclohexane) was added at −60° C. over 15 min. The mixture was warmed to room temperature. A solution of n-BuLi (17.6 ml, 40 mmol, 2.5 in hexane) was added, and the reaction was stirred at room temperature for 1 h. It was cooled to −70° C. and transferred into an acidic ethanol solution (20 ml acetyl chloride and 100 ml ethanol) at 0° C. via a cannula over 1 h period. The resulting mixture was diluted with 400 ml ether and washed with 400 ml 10% HCl solution. The aqueous layer was extracted with ether. The combined organic layer was washed with brine, dried with MgSO4, and concentrated. The residue was purified by chromatography (on silica gel, ethyl acetate/hexane=1/9) to give a brown liquid in 1.17 g. NMR spectra of the product were consistent for the proposed structure.

ORD record

ord-b086ce116a784e448940c86eed99434d

Source dataset

uspto-grants-2005_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06921767B2