Water → Bicyclohexyl

Participants

Reaction Steps

A stirred, ice-cooled (2° C.) solution of 1N lithium aluminum hydride/THF (3.43 mL, 3.43 mmol) under nitrogen was treated dropwise with a solution of the above diimide intermediate (140 mg, 0.55 mmol) in anhydrous tetrahydrofuran (20 mL), stirred for 1 h at room temperature and 7 h at reflux, then cooled on an ice bath. Water (0.30 mL), 15% NaOH (0.30 mL) and water (0.90 mL) were added dropwise together with more tetrahydrofuran to facilitate stirring. The mixture was stirred at room temperature for 15 minutes, filtered through celite, and the filtrate concentrated in vacuo. The residue was dissolved in methylene chloride, loaded onto a silica gel column, and eluted with 3:1 methylene chloride/ethyl acetate to afford 3-methyl-1-(1-methylindol-2-yl)-3-azabicyclo[3.1.0]bicyclohexane (100 mg, 80%), which was then converted to the hydrochloride salt by treating with 2N HCl/ether (82 mg, 80%). MS (M+1) 226.8 1H NMR (DMSO-d6) δ 11.35-11.12 (br s, 1H), 7.52-7.34 (m, 2H), 7.15-6.93 (m, 2H), 6.45-6.34 (m, 1H), 3.92-3.84 (m, 1H), 3.79-3.75 (s, 3H), 3.71-3.64 (m, 1H), 3.63-3.56 (m, 1H), 3.39-3.26 (m, 1H), 2.81 (d, 3H), 2.24-2.16 (m, 1H), 1.91-1.83 (m, 1H), 1.11-1.01 (m, 1H). 13C NMR (DMSO-d6) δ 138.06, 137.98, 127.38, 122.00, 14.21, 120.67, 119.98, 110.28, 102.01, 59.38, 56.47, 40.36, 30.96, 24.26, 22.51.

Provenance & Evidence