Methyl iodide → (4-Isopropoxy-3-methoxy-phenyl)-[cis-8-methoxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]methanone

Participants

Reaction Steps

To a solution of [cis-8-hydroxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methoxy-phenyl)methanone (139 mg, 0.3 mmol) in DMF (4 mL) was added sodium hydride (34 mg, 1.5 mmol). The mixture was stirred at room temperature for 30 minutes. Iodomethane (187 μL, 3.00 mmol) was added. The mixture was stirred at room temperature overnight, then repartitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate (2×). The combined organic layers were washed with water (3×), brine, dried over MgSO4, filtered and concentrated to dryness. The crude material was purified by column chromatography (50-60% ethyl acetate-Hex) to provide (4-isopropoxy-3-methoxy-phenyl)-[cis-8-methoxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]methanone (102 mg). 1H NMR (400 MHz, CDCl3) δ 7.48-7.33 (m, 4H), 7.33-7.28 (m, 1H), 7.01-6.90 (m, 2H), 6.86 (d, J=8.2 Hz, 1H), 4.66-4.46 (m, 2H), 4.12-3.90 (m, 2H), 3.86 (s, 3H), 3.76-3.61 (m, 1H), 3.48 (s, 1H), 3.37 (d, J=4.5 Hz, 3H), 3.21 (t, J=11.8 Hz, 1H), 2.28 (dd, J=39.8, 13.2 Hz, 2H), 2.00 (dd, J=12.6, 2.7 Hz, 1H), 1.85-1.62 (m, 3H), 1.59-1.44 (m, 1H), 1.42-1.33 (m, 7H). ESI-MS m/z calc. 453.25, found 454.5 (M+1)+; Retention time: 1.65 minutes (3 minute run).

Provenance & Evidence