Chlorotrimethylsilane → 15-Ethyl-3-methoxyestra-1,3,5(10),15-tetraen-17-one

Participants

Reaction Conditions

Reaction Steps

A solution of lithium diisopropylamide (7.8 mmol) in dry tetrahydrofuran (3 ml) [prepared at 0° C. from diisopropylamine (2.2 ml; 15.8 mmol) in tetrahydrofuran (3 ml) and butyl lithium (4.9 ml; 1.6M; 7.8 mmol)] was cooled to -78° C. A solution of the 15β-ethyl ketone (6) (495 mg; 1.58 mmol) in dry tetrahydrofuran (12 ml) was slowly added. After 30 min. at -78° C., chlorotrimethylsilane (2.5 ml; 19.7 mmol) was added and stirring was maintained at 0° C. for 15 min. Saturated aqueous ammonium chloride was added. The residue upon work-up (ethyl acetate) (577 mg) was dissolved in dry acetonitrile (20 ml). Palladium(II) acetate (340 mg; 1.51 mmol) was added and the solution was heated to refluxing temperature for 20 min. The solution was cooled to 20° C., filtered, and evaporated. Chromatography of the residue (470 mg) on silica gel (25 g) and eluting with ethyl acetate (1:19) gave 15-ethyl-3-methoxyestra-1,3,5 (10), 15-tetraen-17-one (7) (419 mg; 85% from 6), m.p. 103-106° C. (from chloroform-methanol); [α]D -14° (c 0.9); νmax 1689 cm-1 ; δH 1.11 (3H, s, 13β-Me), 1.20 (3H, t, J 7.6 Hz, 15-CH2CH3), 2.40 (2H, m, 15-CH2CH3), 3.78 (3H, s, 3-OMe), 5.79 br (1H, s, 16-H), 6.64 (1H, d, J 2.8 Hz, 4-H), 6.73 (1H, dd, J 8.3 and 2.8 Hz, 2-H), and 7.22 (1H, d, J 8.3 Hz, 1-H); δc 11.6 (C-152), 21.5 (C-18), 25.6 (C-11), 27.3 (C-7), 28.0 (C-12), 29.2 (C-151), 29.4 (C-6), 37.0 (C-8), 45.3 (C-9), 52.6 (C-13), 55.2 (3-OMe), 57.0 (C-12), 111.6 (C-2), 113.6 (C-4), 125.7 (C-16), 126.2 (C-1), 132.1 (C-10), 137.3 (C-5), 157.5 (C-3), 181.1 (C-15), and 212.2 (C-17) (Found: C, 81.1; H, 8.5%; M+, 310. C21H26O2 requires C, 81.25; H, 8.4%; M, 310).

Provenance & Evidence