Water → 1,2-Dimethylpiperidin-4-one

Participants

Reaction Conditions

Reaction Steps

A 1 M solution of TiCl4 in CH2Cl2 (23 mL, 23 mmol, 1.0 equiv) was added to a flask under Ar and cooled to −15° C. with a MeOH/ice water bath. 3-[(2-Methoxycarbonyl-ethyl)-methyl-amino]-butyric acid methyl ester (5 g, 23 mmol, 1.0 equiv) was added dropwise over a 25 min period as a solution in 75 mL of dry CH2Cl2 to give a dark red mixture that was difficult to stir with a magnetic stir bar. Stirring was continued an additional 1 h and then Et3N (5.1 g, 50.6 mmol, 2.2 equiv) was added dropwise over a 30 min period and then the reaction was stirred an additional 1.5 h at −15° C. The reaction mix was poured into 150 mL of brine and 150 mL of CH2Cl2 was added. After thorough mixing, the pH of the water was brought to 8–9 with Et3N. The mix was filtered and the gel-like solid was washed 3×100 mL CH2Cl2. The filtrate layers were separated and the aqueous layer was washed 3×50 mL CH2Cl2. All of the organic layers were combined and concentrated to a thick red oil. The residue was taken up in 150 mL of concentrated HCl and the solution was refluxed 4 h. The cooled reaction solution was evaporated to dryness and the residue was dissolved in 200 mL of saturated sodium bicarbonate solution. The product ketone was extracted with 2×100 mL of EtOAc. The organic layers were combined and dried over Na2SO4. The product was purified by flash chromatography on SiO2 using pure CH2Cl2 to 4% MeOH in CH2Cl2 as eluent. The product was isolated as an orange oil (1.23 g, 42%); MS, m/z 128=M+1.

Provenance & Evidence