Water → Bicyclohexyl

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.

1. temperatureat reflux
2. temperaturecooled on an ice bath
3. stirringto facilitate stirring
4. stirringThe mixture was stirred at room temperature for 15 minutes
5. filtrationfiltered through celite
6. concentrationthe filtrate concentrated in vacuo
7. dissolutionThe residue was dissolved in methylene chloride
8. washeluted with 3:1 methylene chloride/ethyl acetate

ORD record

ord-6b7c8d6532fc4d268398de90e3274e09

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133159B2