Diethyl Ether → HCID 22875673, compound

To a solution of 103 mg (0.31 mmol) 7β-methyl-5α-4-azapregnan-3,20-dione in 10 ml dry tetrahydrofuran at -40° C. under N2 was added 6 eq methylmagnesium bromide (1.86 mmol) in ether. The reaction was stirred and allowed to warm to RT over 90 minutes. Aqueous ammonium chloride (5 ml) was added and the solvents were evaporated. The residue was partitioned between methylene chloride and water. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated. The crude residue was dissolved in 5 ml dry dimethylformamide and cooled to 0° C. Methyl iodide (10 eq, 3.1 mmol) and sodium hydride (2 eq, 0.6 mmol) were added and the reaction was stirred at RT for 48 hours. Aqueous ammonium chloride was added and the reaction mixture was poured onto 100 ml water and extracted with three 25 ml portions of ethyl acetate. The organic layer was washed with water, brine, dried over magnesium sulfate, and evaporated. The product was purified via HPLC on a 19×300 mm 8 micron silica column using a 5 to 20% isopropanol/hexane gradient at 20 ml/min to yield 51 mg (0.141 mmol, 46% yield) of the title compound.

1. customthe solvents were evaporated
2. customThe residue was partitioned between methylene chloride and water
3. washThe organic layer was washed with brine
4. dry with materialdried over magnesium sulfate
5. customevaporated
6. dissolutionThe crude residue was dissolved in 5 ml dry dimethylformamide
7. temperaturecooled to 0° C
8. stirringthe reaction was stirred at RT for 48 hours
9. extractionextracted with three 25 ml portions of ethyl acetate
10. washThe organic layer was washed with water, brine
11. dry with materialdried over magnesium sulfate
12. customevaporated
13. customThe product was purified via HPLC on a 19×300 mm 8 micron silica column

ORD record

ord-519b07bd7b03425db050f2bfc0156d5d

Source dataset

uspto-grants-1997_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05658922