Diethyl Ether → 3-Hydroxy-2-methoxymethylestra-1,3,5(10)-trien-17-one

To a suspension of 2-dimethylaminomethyl-3-hydroxyestra-1,3,5(10)-trien-17-one (72, 2.0 g, 6.1 mmol) in Et2O (200 mL) was added iodemethane (10 mL, 161 mmol) and stirred for 20 h at room temperature. The precipitate was collected by filtration and washed with Et2O. The solid was dissolved in MeOH (50 mL) and added potassium hydroxide (5.0 g, 85%, 76 mmol), and stirred for 3 h at reflux condition. After the reaction mixture was cooled to room temperature, solvent was evaporated at reduced pressure until half volume. The reaction mixture was acidified with 5 N HCl at 0° C., and extracted with Et2O. The combined organic layers were washed with H2O, saturated aqueous NaCl, and then dried (Na2SO4). The desiccant was filtered and the solvent was evaporated at reduced pressure. The residue was purified by column chromatography (silica gel) using CHCl3 :EtOAc (15:1→10:1, v/v) to afford 1.34 g of 74 (88% yield) mp: 149-151° C.

1. additionwas added iodemethane (10 mL, 161 mmol)
2. filtrationThe precipitate was collected by filtration
3. washwashed with Et2O
4. dissolutionThe solid was dissolved in MeOH (50 mL)
5. stirringstirred for 3 h
6. temperatureat reflux condition
7. temperatureAfter the reaction mixture was cooled to room temperature
8. customsolvent was evaporated at reduced pressure until half volume
9. customwas acidified with 5 N HCl at 0° C.
10. extractionextracted with Et2O
11. washThe combined organic layers were washed with H2O, saturated aqueous NaCl
12. dry with materialdried (Na2SO4)
13. filtrationThe desiccant was filtered
14. customthe solvent was evaporated at reduced pressure
15. customThe residue was purified by column chromatography (silica gel)

ORD record

ord-a8aa778cad5a40bdb12eb803af4c4dda

Source dataset

uspto-grants-2000_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06046186