Hydrochloric Acid → (RS)-1-(6-Hydroxy-2,3-dihydro-benzofuran-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol Hydrochloride

Participants

Reaction Conditions

Reaction Steps

(RS)-1-(6-methoxy-2,3-dihydro-benzofuran-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol (1.24g, 3.37 mmol) dissolved in 35 ml of CH2Cl2 was cooled to −8° C. and 1M BBr3—CH2Cl2 solution (6.8 ml, 2 eq.) was added dropwise under argon. The violet suspension was allowed to warm to room temperature and then stirred for 30 minutes. The reaction was then cooled to 0° C. and MeOH (9 ml) was added to quench the reaction, followed by satd. NaHCO3 (50 ml). The organic phase was separated and the aqueous phase was extracted with CH2Cl2 (2×50 ml). The combined organic extracts were dried with Na2SO4 then filtered and evaporated. The resulting yellow foam was chromatographed over SiO2 (Merck 230-400 mesh) eluting with MeOH—CH2Cl2 (1:19) followed by MeOH—CH2Cl2 (1:9) to provide a yellow foam which was dissolved in MeOH (5 ml) and treated with 1N HCl (3.4 ml) to provide (RS)-1-(6-hydroxy-2,3-dihydro-benzofuran-2-ylmethyl)-4-(methyl-benzyl)-piperidin-4-ol hydrochloride (0.92g, 70%) as a white solid and mixture of E/Z isomers. Mp. 203-205° C. MS: m/e=354.3(M+H+)

Provenance & Evidence