1-benzyl-4-(methoxymethylidene)piperidine

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of di-isopropylamine (11.1 g, 15.4 mL, 110 mmol) in anhydrous tetrahydrofuran (100 mL) was cooled to 0° C. under a nitrogen atmosphere. A solution of n-butyl lithium in hexanes (2.5 M, 44 mL, 110 mmol) was added dropwise with stirring. The pale yellow solution was stirred for 15 minutes at 0° C., then transferred via cannula to a suspension of methoxymethyl-triphenylphosphonium chloride (37.7 g, 110 mmol) in dry tetrahydrofuran (300 mL) stirred at -20° C. After 30 minutes, the reaction mixture was cooled to -40° C. and a solution of 1-benzylpiperid-4-one (18.9 g, 18.5 mL, 100 mmol) in anhydrous tetrahydrofuran (100 mL) was added dropwise over 15 minutes. The reaction mixture was warmed gradually to ambient temperature over 23 h. The reaction mixture was then poured onto water, mixed and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate and filtered; solvent was removed in vacuo. Column chromatography (ethyl acetate) gave starting piperidine (Rf =0.7, 0.5 g) and the product (Rf =0.51, 11.6 g), an orange-yellow liquid:1HNMR:7.4-7.25(m,5H), 5.8(s,1H), 3.5(s,2H), 3.45(s,3H), 2.5-2.3(m,5H), 2.05(t,2H,J=7); MS:217. The pale yellow solution was stirred for 15 minutes at 0° C. stirred at -20° C The reaction mixture was warmed gradually to ambient temperature over 23 h The reaction mixture was then poured onto water mixed extracted three times with ethyl acetate The combined organic layers were dried over magnesium sulfate filtered solvent was removed in vacuo Column chromatography (ethyl acetate) gave