N,N-Dimethylmethyleneammonium Iodide

Typical Procedure:
To a cold (-20 °C) solution of diisopropylamine (50 mg, 0.492 mmol) in THF (630　µL) is added the solution of n-butyllithium in hexane (294 µL of the 1.67 M solution, 0.491 mmol). The solution is stirred for 15 min at that temperature, then cooled to -78 ℃ and the solution of 1 (91.3 mg, 0.447 mmol) in THF (400　µL) is added. HMPA (319 mg, 1.78 mmol) is added to the solution of the lithium enolate, and the resulting solution is transferred via cannula to a cold (-78 °C) suspension of the Eschenmoser's salt (200 mg, 1.08 mmol) in THF (1 mL). The reaction mixture is allowed to reach rt with stirring, when the yellow suspension turned into solution. The reaction is quenched with saturated aqueous NaHCO₃ (10 mL) and the product is extracted with ethyl acetate (4 x 25 mL). The organic extract is washed with brine, dried over anhydrous MgSO₄, filtered and concentrated under reduced pressure. The crude residue (430 mg) is dissolved in diethyl ether (3 mL), methyl iodide (1 mL, 16.28 mmol) is added and the reaction mixture is stirred at rt for 2 hours. The solution of NaOAc (1.2 g) in water (7 mL) is added and the reaction mixture is vigorously stirred for 1 hour. The mixture is diluted with hexane (80 mL) and water (10 mL), the phases are separated and the aqueous phase is extracted with hexane (2 x 10 mL). The combined extract is thoroughly washed with water, dried over anhydrous MgSO₄, filtered and concentrated under reduced pressure. Purification of the crude organic residue (107 mg) by column chromatography (gradient elution with hexane : diethyl ether = 95 : 5 → 9 : 1) affords 2 (28 mg, Y. 53%).