Toluene → 1-(1-Benzylpiperidin-4-yl)ethanone

Participants

Reaction Steps

A solution of 47.32 g 1-benzyl-N-methyl-N-methoxy-piperidine-4-carboxamide in 1.5 L anhydrous ether in a 2-L 3-neck round-bottom flask fitted with a nitrogen bubbler, an overhead stirrer, and an addition funnel was cooled with an ice-acetone bath, and was treated with 270 mL of a 1.53M solution of methylmagnesium bromide in 1:3 THF:toluene with stirring over 70 minutes. After stirring in an ice bath for additional two hours, the mixture was quenched with 15 mL EtOAc, stirred for 10 minutes, and then poured into 2 L of ice water. After adjusting the pH to 8˜9, the layers were separated. The mixture was extracted with 4×250 mL ether, the combined ether solution was washed with 300 mL each of water and saturated brine, and then dried over Na2SO4. Removal of solvent under reduced pressure gave 40.68 g of crude product. This material was purified by flash chromatography on silica gel eluting with 25%˜40% EtOAc in hexanes with 1% Et3N to give 39.533 g of the title compound as a yellowish liquid. RF: 0.20 (20% EtOAc in hexanes with 1% (v/v) Et3N). 1H NMR (500 MHz, CDCl3): δ7.32˜7.35 (m, 4H), 7.25˜7.30 (m, 1H), 3.53 (s, 2H), 2.91˜2.95 (m, 2H), 2.28˜2.34 (m, 1H), 2.16 (s, 3H), 2.01˜2.07 (m, 2H), 1.83˜1.88 (m, 2H), 1.66˜1.74 (m, 2H).

Provenance & Evidence