Chlorotrimethylsilane → (2RS,3SR)-3-(2-Ethoxyphenoxy)-2-mesyloxy-3-phenyl-1-(trimethylsilyloxy)propane

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Reaction Conditions

Reaction Steps

3-(2-Ethoxyphenoxy)-2-hydroxy-3-phenylpropanol from Example 2 (1.44 g, 5 mmole) and triethylamine ((0.77 mL, 5.5 mmole) were dissolved in ethyl acetate (15 mL) and cooled to −17° C. Trimethylsilyl chloride (0.64 mL, 5.0 mmole) dissolved in ethyl acetate (5 mL) was added over 10 minutes keeping the temperature below −15° C. A white precipitate formed during this addition. The mixture was stirred below −15° C. for 15 minutes. Triethylamine (0.8 mL, 5.7 mmole) was added, followed by methanesulfonyl chloride (0.46 mL, 6.0 mmole) dissolved in 5 mL of ethyl acetate, keeping the temperature below −15° C. The mixture was stirred below −15° C. for 15 minutes. Pentane (20 mL) was added and the solids were removed by filtration. The filtrate was concentrated under vacuum to a cloudy oil. The oil was chromatographed on silica (230-400 mesh) eluting with 4:1 heptane-ethyl acetate. The product-containing fractions were concentrated to yield 2.00 g (91.2%) of the title compound as an oil that solidified on standing; mp 80-82.5° C.; 1H NMR (400.13 MHZ, CDCl3) d 0.17 (s, 9H), 1.50 (t, J=6.8 Hz, 3H), 3.06 (s, 3H), 3.77 (dd, J=11, 6, 1H), 4.00 (dd, J=11, 6, 1H), 4.10, (q, J=6.8, 2H), 5.07, (m, 1H), 5.51 (d, J=4.4, 1H), 6.75 (m, 2H), 6.91 (m 2H), 7.2-7.49 (m, 5H); 13C NMR (100.62 MHZ, CDCl3) d 0.0, 15.66, 38.87, 61.57, 64.88, 79.90, 85.20, 113.97, 116.99, 121.32, 122.79, 128.26, 129.09, 129.14, 136.75, 147.72, 149.95; MS (ei) m/e 438.

Provenance & Evidence