2,5(10)-ESTRADIEN-3-OL-17-ONE 3-METHYL ETHER synthesis

Yield: 87%

Reaction Conditions:

Stage #1:3-methoxy-17-hydroxyestra-2,5⁽¹⁰⁾-diene with 2,6-di-tert-butyl-4-methyl-phenol;cyclohexanone;aluminum isopropoxide in toluene at 108 - 110; for 1 h;
Stage #2: with water in toluene at 20 - 25; for 1 h;

Steps:

1
To a stirred solution of 106.3 g (0.52 mmol) of aluminum isopropoxide in 2000 ml of dry toluene 720 ml of cyclohexanone, 0.35 g of 2,6-ditert-butyl-4-methyl-phenol and 100 g (0.307 mol) 3-methoxy-17-hydroxy-estra-2,5(10)-diene were added, then the reaction mixture was stirred at 108-110 ⁰C for 1 h. The reaction was followed by TLC. After completion of the reaction the mixture was cooled to 20-25 ⁰C, 200 ml of water was added and the so obtained mixture was stirred for 1 h. The precipitated aluminum hydroxide was filtered off and the filtrate was concentrated to a volume of 250 ml under reduced pressure. A mixture of 200 ml of methanol and 100 ml of water was added to this concentrated warm - about 60 ⁰C - solution, the obtained suspension was cooled to 20-25 °C and stirred for 1 h. The precipitated crystalline product was filtered off and dried below 40 ⁰C in vacuum to yield 76.4 g (87%) of the title compound. Purity: min. 98% (HPLC) Melting point: 106-110 °C.

References:

RICHTER GEDEON VEGYÉSZETI GYÁR RT. WO2007/66158, 2007, A2 Location in patent:Page/Page column 8