Nitrogen → Lithium diisopropylamide

Participants

Reaction Steps

A solution of lithium diisopropylamide was prepared by dropwise addition of n-BuLi (Aldrich 1.6M in hexane, 228 mL, 0.365 mol) to a solution of diisopropylamine (Aldrich, 51.6 g, 0.51 mol) in a mixture of dry THF (700 mL) and dry HMPA (Aldrich, 40 mL) kept at 30°-40°. The solution was then cooled to -70° and a solution of ethyl N-benzylidene-l-alaninate 10A, 74.9 g, 0.365 mol) was added dropwise to the solution allowing the reaction mixture warm to -20° for several min. The resulting red solution was then cooled to -70°. 2-(2-Iodoethoxy)tetrahydro-2-H-pyran (10B, 98.1 g, 0.383 mol) was then added to the solution at such a rate that the temperature in the reaction mixture did not rise above -65°. The solution was allowed to warm slowly to RT and stirred for 14 h. The volume of the solution was reduced to 300 mL by a stream of dry N2 during the last few hours to facilitate the final workup. The reaction was quenched with satd. NaCl (800 mL) and diluted with Et2O (800 mL). The Et2O was removed and the aqueous layer extracted with hexane (500 mL). The Et2O and hexane layers were combined and dried (Na2SO4). The solution was filtered and the solvent removed to give 124 g of of crude red oil. Bulb to bulb distillation (in 1% aq. NEt3 washed glassware) (210° bath temperature/0.3 mm) gave 95 g of ethyl 2-benzylideneamino-2-methyl-4-((tetrahydro-2Hpyran-2-yl)oxy)butyrate which was homogeneous by vpc and gave acceptable NMR and mass spectra. It was stored under N2 in the refrigerator and was used without further purification.

Provenance & Evidence