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

Participants

Reaction Steps

Under an atmosphere of argon, 2,2,6,6-tetramethyl piperidine (6.85 g, 48.4 mmoles) was added to a solution of n-butyl lithium (18.0 ml. 44.4 mmoles, 2.5M in hexane) diluted with THF (50 ml) at 0° C. to form LTMP. In a separate flask, a solution of the product from STEP 2 (5.0 g, 20.2 mmoles), dibromomethane (7.7 g, 44.4 mmoles), and THF (50 ml) was cooled to −78° C. After 30 minutes, LTMP solution was added to above solution via a double-ended needle over 20 minutes. After 10 minutes, a lithium bis(trimethylsilyl)amide solution (40.3 ml, 40.3 mmoles, 1 M in THF) was added to the reaction over 15 minutes at −78° C. The reaction was warmed to −20° C. and then cooled to −78° C. A solution of s-butyl lithium (62 ml, 80.6 mmoles, 1.3M in cyclohexane) was added at −60° C. over 20 minutes. The reaction was warmed to −20° C. A solution of n-butyl lithium (16.1 ml, 40.3 mmoles, 2.5M in hexane) was added. The reaction was allowed to warm to room temperature, and stirred for 1 hour. The reaction was cooled to −78° C. and quenched into a stirred anhydrous acidic ethanol solution at 0° C. over 40 minutes. The resulting mixture was diluted with ether (800 ml), and washed with 1N HCl solution (350 ml). The aqueous layer was extracted with ether (3×80 ml). The combined ethereal extracts were dried with MgSO4, filtered and concentrated. Chromatography of the residue (SiO2; ethyl acetate/hexane=8/92) gave the desired product as a pale brown oil (1.6 g; 30% yield). The 1H NMR spectrum was consistent with the proposed structure.

Provenance & Evidence