Ethyl Acetate → 10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4-f]quinolin-5-ol

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Reaction Steps

The product from Example 5 (75.2g, 98% potent, 0.23 mol) in CH2Cl2 (3.8 L) under N2 was cooled to −78° C. and treated with 1M DIBAL in heptane (328 ml) dropwise over 1-1.5 hours while maintaining the temperature below −76° C. The reaction was monitored by HPLC and/or TLC until the reaction was complete (1.5 hours). EtOAc (1 L) and a saturated Rochelle salt solution (2 L) was added. The mixture was allowed to warmed to room temperature and stirring was continued until the organic and aqueous layers clearly separated. The organic layer was then washed with brine (0.5L), dried over Na2SO4 and concentrated to a thick suspension (approx. 300 g). The suspension was then cooled to 0° C., filtered and washed with cold EtOAc. The wet cake was dried under reduced pressure at 40° C. to provide the title compound (59.4 g, 99% potent, 80% potency adjusted yield). A small reference sample was recrystallized from EtOAc. mp 184-5° C.; Anal. Calcd for C20H21NO3: C, 74.28; H, 6.55; N, 4.33. Found C, 73.32; H, 6.51; N, 4.24. 1H NMR [(CD3)2SO] δ1.08 (3H, s), 1.26 (3H, s), 2.23 (3H, s), 3.86 (3H, s), 5.42 (1H, s), 6.11 (1H, s), 6.56 (1H, d), 6.61 (1H, d), 6.64 (1H, d), 6,71 (1H, d), 6.94 (1H, d), 7.07 (1H, t), 7.99 (1H, d); 13C NMR [(CD3)2SO] δ22.8, 28.1, 29.9, 49.6, 55.6, 89.8, 105.4, 110.8, 113.0, 113.9, 116.2, 117.0, 126.6, 127.2, 128.2, 130.0, 132.5, 145.4, 150.5, 156.5; FAB HRMS: calcd for C20H21NO3: 323.1521. Observed 323.1514.

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