14814-17-6

[4-(2-Hydroxyethoxy)phenyl]phenylmethanone is an intermediate in the synthesis of E-Ospemifene (O703005). E-Ospemifene is the E-isomer of Ospemifene (O703000) and is useful for lowering serum cholesterol. It acts as an anti-atherosclerotic and is also estrogen-like.

I) Synthesis of Glycol to Benzophenone Ether: 520g of Diethylene Glycol Diethyl Ether, 286g of 4-Hydroxy Benzophenone (Purity >98wt%) and 0.8g of Powdered Potassium Hydroxide were added to a 2L laboratory autoclave. The system was pressure tested for 30 minutes using dry nitrogen gas. After the pressure was reduced to atmospheric pressure, the reaction mixture was heated to 120°C under nitrogen protection. Subsequently, 95.4 g of ethylene oxide was slowly passed over a period of 1 hour, controlling the maximum internal pressure to not exceed 4 bar. After the ethylene oxide addition was completed, the reaction was continued until the pressure remained constant for at least 30 minutes. The reaction mixture at elevated temperature was drained from the autoclave and neutralized with 5 wt% aqueous hydrochloric acid solution, then poured into 2 L of ice water and the product was crystallized by continuous stirring. The resulting solid was separated by vacuum filtration, washed with ice water and dried under vacuum at 40 °C and 10 mbar absolute pressure. The filtrates were combined and concentrated to 20% of the original volume in a rotary film evaporator, and the product precipitated again was dried by vacuum filtration, washed with ice water and dried in the same way. The total yield was 82% of the theoretical value.

[1] Patent: US2004/249186, 2004, A1. Location in patent: Page 7