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

Participants

Reaction Conditions

Reaction Steps

To 8-(3-methoxybenzyl)-1,4-dioxa-8-azaspiro[4.5]decane (2.3 g, 8.7 mmol) from Step A above was added an ice-cold solution of concentrated hydrochloric acid (40 mL). The suspension was stirred at 0° C. for 5 min and then allowed to warm to ambient temperature. After 0.5 h, the homogeneous solution was poured into a 0° C. sodium hydroxide solution (21.5 g in 200 mL of water) and then extracted with methylene chloride (2×150 mL). The combined organic layers were dried over 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 (1.4 g, 73%) as a colorless oil: 1H NMR (DMSO-d6, 500 MHz) δ 7.25-7.19 (m, 1H), 6.92-6.91 (m, 2H), 6.85-6.83 (m, 1H), 3.75 (s, 3H), 3.58 (s, 2H), 2.69-2.65 (m, 4H), 2.37-2.32 (m, 4H).

Provenance & Evidence