Hydrochloric Acid → 1-[(3-Methoxyphenyl)methyl]piperidin-4-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 8-(3-methoxybenzyl)-1,4-dioxa-8-azaspiro[4.5]decane (16.0 g, 60.76 mmol) from Step A above was added an ice-cold solution of concentrated hydrochloric acid (320 mL). The suspension was stirred at 0° C. for 5 min and then allowed to warm to ambient temperature. After 1 h, the homogeneous solution was poured into a sodium hydroxide solution (21.5 g in 200 mL of water) at 0° C. and then extracted with methylene chloride (2×150 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by silica gel chromatography (methylene chloride to 1:1 ethyl acetate/methylene chloride) gave 1-(3-methoxybenzyl)piperidin-4-one (11.0 g, 83%) as a colorless oil: 1H NMR (CDCl3, 400 MHz) δ 7.28-7.22 (m, 1H), 6.97-6.90 (m, 2H), 6.82 (dd, J=2.1, 7.9 Hz, 1H), 3.82 (s, 3H), 3.60 (s, 2H), 2.75 (t, J=6.1 Hz, 4H), 2.46 (t, J=6.1 Hz, 4H); ESI MS (m/z) 220 [M+H].

Provenance & Evidence