Methanol → HCID 11587638, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (2SR,3SR)-2-hydroxy-3-(1H-indol-1-yl)-3-(4-methoxyphenyl)-N-methylpropanamide (900 mg, 2.8 mmol) in anhydrous tetrahydrofuran (50 mL) at room temperature under nitrogen was added dropwise a solution of borane-tetrahydrofuran complex (1.0 M in tetrahydrofuran, 13.9 mL, 13.9 mmol) and the mixture heated to reflux for 3 hours. The reaction mixture was then cooled to 50° C., methanol (20 mL) was added, and the mixture stirred at 50° C. for 1 hour. The cooled reaction mixture was then concentrated under reduced pressure to afford a white solid. Purification by flash chromatography (silica, 15% methanol/dichloromethane) afforded 272 mg (32%) of (1SR,2RS)-1-(1H-indol-1-yl)-1-(4-methoxyphenyl)-3-(methylamino)propan-2-ol as a yellow syrup. The product was dissolved in absolute ethanol (4 mL), a solution of hydrogen chloride (4 M in 1,4-dioxane, 0.28 mL, 1.12 mmol) added, the solution stirred for 10 minutes then concentrated under reduced pressure to afford a white foam. Crystallization from 1: 1: 1 v/v absolute ethanol : diethyl ether: hexane (12 mL) at −35° C. afforded 81.3 mg (8%) of (1SR,2RS)-1-(1H-indol-1-yl)-1-(4-methoxyphenyl)-3-(methylamino)propan-2-ol hydrochloride as a hygroscopic white solid. MS (ES) m/z 311.3 ([M+H]+); HRMS: calcd for C19H22N2O2+H+, 311.17540; found (ESI, [M+H]+), 311.176.

Provenance & Evidence