o-Methylvalerolactim → Methyl 2-[(4-fluorophenyl)-(2-methoxy-3,4,5,6-tetrahydro-pyridin-3-yl)-methyl]-4-methyl-3-oxo-pentanoate

Participants

Reaction Conditions

Reaction Steps

6-Methoxy-2,3,4,5-tetrahydropyridine (102.7 g, 0.91 mole) was added over 25 min to a solution of lithium diisopropylamine (1.8 M, 505 mL, 0.91 mole) in THF (1.2 L) stirring at −60° C. under nitrogen. After stirring at −60° C. for 1 h, methyl 3-(4-fluorophenyl)-2-isobutyrylacrylate (175 g, 0.70 mole) was added over 75 min keeping the temperature below −50° C. The reaction was quenched with saturated ammonium chloride (750 mL) after the reaction had stirred at −60° C. for 35 min. After the reaction mixture had warmed to room temperature, ethyl acetate was added and the mixture transferred to a separatory funnel. The mixture was extracted with ethyl acetate (2×1 L). The combined organic layers were washed with 50% saturated ammonium chloride solution, water, and brine; dried over magnesium sulfate; and concentrated in vacuo to afford methyl 2-[(4-fluorophenyl)-(2-methoxy-3,4,5,6-tetrahydro-pyridin-3-yl)-methyl]-4-methyl-3-oxo-pentanoate (271 g).

Provenance & Evidence