Reaction Steps
A toluene (10 mL) solution of 2-Et-3-O-MOM estradiol 53 (170 mg, 0.5 mmol) was treated with sodium hydride (80 mg, 2 mmol) and then brought to reflux for 0.5 h prior to addition of 2-(methoxy)ethyl bromide (141 μL, 1.5 mmol). The reaction was refluxed for 14 h then treated with further aliquots of sodium hydride (80 mg, 2 mmol) and 2-(methoxy)ethyl bromide (141 μL, 1.5 mmol) before refluxing for a further 8 hours after which time no residual starting material remained. The reaction was then cooled to room temperature, diluted in ethyl acetate (30 mL) and then treated with saturated ammonium chloride (20 mL). The organic layer were separated, washed with water (2×20 mL), brine, dried and evaporated. The desired ether 54, a clear colourless oil (128 mg, %) was isolated by column chromatography (gradient 0 to 20% ethyl acetate in hexane) and showed δH (400 MHz, CDCl3, ref. TMS=0) 7.08 (1H, s, ArH), 6.78 (1H, s, Ar, H), 5.17 (2H, s, OCH2), 3.67-3.74 (1H, m), 3.52-3.56 (2H, m), 3.48 (3H, s, OMe), 3.43 (1H, dd, J 8.6 and 8.2, CHO), 3.40 (3H, s, OMe), 2.78-2.86 (2H, m, 6-CH2), 2.63 (2H, q, J 7.4, CH2Me), 2.37-2.44 (1H, m), 2.14-2.22 (1H, m), 2.01-2.11 (2H, m), 1.83-1.90 (1H, m), 1.23-1.72 (8H, m), 1.19 (3H, t, J 7.4, CH2Me) and 0.81 (3H, s, 18-CH3) δC 152.6, 135.0, 133.2, 130.3, 126.1, 114.0, 94.3, 89.6, 72.3, 69.6, 59.2, 56.0, 50.4, 44.1, 43.5, 38.7, 38.3, 29.7, 28.3, 27.4, 26.6, 23.6, 23.2, 15.0 and 11.7.
