Reaction Steps
A mixture of 7-benzyl-3-tributylstannyl-1-oxa-7-azaspiro[4,5]dec-3-ene (Desc. 3; 1.68 g, 3.24 mmol), 2-bromoanisole (0.80 ml, 6.42 mmol), lithium chloride (0.94 g, 22 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.37 g, 0.32 mmol) in toluene (40 ml) was degassed then heated at reflux overnight (17 hours). The mixture was allowed to cool, filtered and concentrated in vacuo. The residue was dissolved in ether (100 ml) and extracted with 2M hydrochloric acid (100 ml then 25 ml). The aqueous phases were washed with more ether (100 ml), combined, basified with 4 M sodium hydroxide (70 ml) and extracted with ethyl acetate (2×50 ml). The organic phases were washed with brine (50 ml), dried (MgSO4) and concentrated. The residue was purified by flash chromatography, eluting with ethyl acetate/hexane (1:2 then 1:1), to give 7-benzyl-3-(2-methoxyphenyl)-1-oxa-7-azaspiro[4,5]dec-3-ene (0.67 g, 62%. This oil was dissolved in isopropanol and treated with excess ethereal hydrogen chloride. The mixture was concentrated in vacuo and recrystallised from isopropanol/diethyl ether to afford the title compound, m.p. 198°-201° C.; (Found: C, 69.61; H, 6.85; N, 3.62. C22H26ClNO2 0.4H2O requires C, 69.70; H, 7.13; N, 3.69%); δH (360MHz, D2O) 1.78-2.22 (4H, m), 2.98-3.26(3H, m), 3.58 (1H, m), 3.89 (3H, s, ArOCH3), 4.29 (1H, br d, NCHAHBPh), 4.43 (1H, d, J 13.1Hz, NCHAHBPh), 5.00 (2H, m, 2-CH2), 6.33 (1H, br, s, 4-H), 7.02 (1H, t, J 7.5Hz, ArH), 7.11 (1H, d, J 8.4Hz, ArH), 7.16 (1H, m, ArH), 7.39 (1H, m, ArH), 7.53 (5H, m, PhH); m/z (ES+) 336 ([M+H]+).
