Reaction Steps
A suspension of the product from step A (6.82 g, 10.3 mmol), methyl iodide (4.37 g, 30.8 mmol) and K2CO3 (3.05 g, 30.8 mmol) in acetone (200 mL) at ambient temperature was stirred for 18 hours. At the end diluted with ethyl acetate (200 mL), washed with water (100 mL), brine (100 mL) and dried. Chromatography with gradient elution (SiO2) using hexanes, ethyl acetate (90:10 to 70:30) afforded the compound of Step B as the major product (5.52 g, 8.1 mmol, 79%, Rt=2.3 minutes C18 LC) as white solid. MS [M+H]=678. 1H NMR (CD3OD) δ 7.82 (d, J=8.1 Hz, 1H), 7.73 (d, J=8.9 Hz, 1H), 7.52 (d, J=9.2 Hz, 1H), 7.48 (m, 4H), 7.34 (m, 3H), 7.21 (m, 6H), 3.91 (m, 1H), 3.76 (m, 4H), 2.88 (m, 1H), 2.70 (m, 1H), 1.71 (s, 3H), 0.94 (s, 9H). A minor product characterized as the O-methyl derivative had the following characteristics. MS [M+H]=678. 1H NMR (CD3OD) δ 7.82 (d, J=8.1 Hz, 1H), 7.95 (d, J=5.1 Hz, 1H), 7.52 (d, J=9.2 Hz, 1H), 7.48 (m, 4H), 7.34 (m, 3H), 7.21 (m, 6H), 3.91 (m, 1H), 3.76 (m, 4H), 2.88 (m, 1H), 2.70 (m, 1H), 1.71 (s, 3H), 0.94 (s, 9H). The ratio of the N-methyl derivative to the O-methyl derivative was approximately 9:1.
