Reaction Steps
To a solution of 2-{3-[3-(4-acetyl-5-benzyloxy-2-ethylphenoxy)propoxy]-2-propyl-phenoxy}benzoic acid methyl ester (3.04 g, 5.09 mmol) in tetrahydrofuran (50 mL) cooled to −78° C. was added a solution of 1 M lithium hexamethyldisilazide in tetrahydrofuran (11.2 mL, 11.2 mmol) portion wise. After stirring for 20 min, trimethylsilyl chloride (2.6 mL. 20 mmol) was added and the mixture warmed to 0° C. and stirred for 30 min. The mixture was evaporated in vacuo and the residue dissolved in hexane. The resulting solution was filtered and concentrated in vacuo. The residue was dissolved in tetrahydrofuran (50 mL), cooled to 0° C., and treated with N-chlorosuccinimide (750 mg, 5.6 mmol). The mixture was warmed to room temperature and stirred for 30 min, then heated at reflux for 2 h. The mixture was cooled to room temperature and treated with water (4 mL) and a solution of 1 N tetra-n-butylammonium fluoride in tetrahydrofuran (6 mL). After stirring for 15 min the mixture was diluted in ether and washed once with water, once with saturated sodium chloride solution, dried (sodium sulfate), filtered, and concentrated in vacuo. Chromatography (silica gel, 10% ethyl acetate/90% hexane) of the residue provided 1.94 g (60%) of the title compound as a white solid. 1H NMR (CDCl3) δ 7.89 (d, J=8 Hz, 1H), 7.77 (s, 1H), 7.40 (m, 6H), 7.12 (d, J=9 Hz, 1H), 7.06 (d, J=8 Hz, 1H), 6.80 (d, J=8 Hz, 1H), 6.66 (d, J=8 Hz, 1H), 6.49 (s, 1H), 6.43 (d, J=8 Hz, 1H), 5.15 (s, 2H), 4.68.(s, 2H), 4.20 (q, J=6 Hz, 4H), 3.82 (s, 3H), 2.65 (t, J=7 Hz, 2H), 2.59 (q, J=7 Hz, 2H), 2.32 (quintet, J=6 Hz, 2H), 1.54 (hextet, J=8 Hz, 2H), 1.16 (t, J=8 Hz, 3H), 0.89 (t, J=7 Hz, 3H); TOF MS ES+ exact mass calculated for C37H40ClO7 (p+1): m/z=631.2463. Found: 631.2470; IR (CHCl3, cm−1) 2964, 1720, 1603, 1461. Anal. Calcd for C37H39ClO7: C, 70.41; H, 6.23. Found: C, 0.04; H, 5.97.
