Potassium Hydroxide → HCID 11182960, compound

Participants

Reaction Steps

N-((1R,2R)-2-amino-1,2-diphenylethyl)-4-methylbenzenesulfonamide (0.333 g, 0.908 mmol) and benzene ruthenium(II) chloride dimer (0.113 g, 0.226 mmol) in 80 mL isopropanol were stirred at 80° C. for 30 minutes, then cooled to room temperature. A solution of 8-methoxy-2-tetralone (4.0 g, 23 mmol) in isopropanol (400 mL) was added, followed by potassium hydroxide (0.038M in isopropanol, 120 mL, 4.56 mmol). The reaction mixture was stirred at 50° C. for 1.5 hours, at which time the starting material had been consumed. The isopropanol was evaporated, the residue was taken up in ethyl acetate and washed with water and brine. The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was chromatographed on silica gel (15 to 30% ethyl acetate-hexane, eluant) to afford 3.0 g (74% yield) of the title compound as a fluffy off-white solid. Analytical chiral HPLC (Chiralcel OJ 4.6×25 mm, 20% isopropanol/hexane, 23° C., 0.5 mL/min) showed the isolated material to be >98% ee. 1H NMR (300 MHz, DMSO-d6) δ 7.04 (t, J=7.8 Hz, 1H), 6.68 (m, 2H), 4.72 (d, J=3.7 Hz, 1H), 3.87 (m, 1H), 3.74 (s, 3H), 2.57-2.91 (m, 3H), 2.33 (m, 1H), 1.81 (m, 1H), 1.59 (m, 1H). MS (DCI+) m/z 196 (M+NH4)+.

Provenance & Evidence