【Yoshida, M. et al. ARKIVOC. 2003, (vi) 36.】
3-Methoxy-17-trimethylsiloxy-1,3,5(10)-16-estratetraene. A 125-mL, two-necked round-bottomed flaskequipped with a reflux condenser and a magnetic stirrer is purged with argonand charged with 6.8 g (0.024 mol) of estrone 3-methyl ether, 50 mL of drybenzene, and 4.0 mL (2.9 g, 0.029 mol) of triethylamine. The solution is stirred, 4.9 mL (5.6 g,0.025 mol) of trimethylsilyl triflate isadded through a syringe, and the mixture is refluxed for 1.5 hr. The reactionmixture is allowed to cool to room temperature, whereupon it separates into twolayers. Dry hexane (40 mL)is added, and the upper hexane–benzene layer is separated, washed successivelywith saturated sodium bicarbonate and water, andthen dried over magnesium sulfate. The drying agentis removed by filtration, and the filtrate is transferred to a 125-mL, round-bottomed, tared flask. The solution isevaporated to a constant weight with a rotary evaporator, initially atwater-aspirator pressure and then at 0.5–1 mm,to leave 8.6 g(100%) of pale-yellow enol trimethylsilylether. This material is used immediately in Part C without purification.
16α-Fluoro-3-methoxy-1,3,5(10)-estratrien-17-one (16α-fluoroestrone 3-methyl ether). The 125-mL, round-bottomed flaskcontaining the enol silyl ether from Part B is purged with argon, and 50 mL of dry dichloromethane is added. N-Fluoropyridiniumtriflate (6.5 g,0.026 mol) is added in one portion, and the mixture is stirred at 20–25°C for 8 hr. The reaction mixture ispoured into water and extracted with three 60-mL portionsof dichloromethane. The combined organicextracts are washed with saturated sodium bicarbonateand then with water, and dried over magnesium sulfate.The drying agent is removed by filtration and the solution is evaporated todryness with a rotary evaporator. The resulting pale-yellow solid iscolumn-chromatographed on silica gel (250 g, 60 × 4.5-cm column) using dichloromethane eluant to give 950mg (14%) of estrone3-methyl ether starting material and 4.8 g (66%) of 16α-fluoroestrone 3-methylether as a colorless solid, mp 157°C.
【Umemoto,T; Tomita, K; Kawada, K. Organic Syntheses.Coll. Vol. 8, 286.】