Ammonium Chloride → [{(1S,3R,20S)-1,3-dihydroxypregna-5,7,16-triene-20-yl}oxy]-N-(2,2,3,3,3-pentafluoropropyl)acetamide

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Reaction Steps

Under a nitrogen atmosphere, (1S,3R,20S)-1,3-bis(tert-butyldimethylsilyloxy)-20-hydroxypregna-5,7,16-triene (30.0 g) was dissolved in tetrahydrofuran (630 mL), and 0.55 mol/L potassium bis(trimethylsilyl)amide solution in toluene (244 mL) was added thereto dropwise at −10° C. After stirring the resulting mixture for 30 minutes, a solution of 2-bromo-N-(2,2,3,3,3-pentafluoropropyl)acetamide (15.9 g) obtained in Example 3 in tetrahydrofuran was added thereto dropwise over 20 minutes at −15° C., and the resulting mixture was continued to be stirred at the same temperature for 30 minutes. Aqueous ammonium chloride solution and ethyl acetate were added to the reaction solution to carry out extraction, and the organic layer was sequentially washed with water and brine, followed by concentration under reduced pressure. Further, ethyl acetate was removed by azeotropic distillation with methanol under reduced pressure. The obtained concentrated residue was then dissolved in N,N-dimethylacetamide (300 mL), and the resulting mixture was added to a solution of 75% aqueous tetra n-butylammonium fluoride solution (51 mL) and acetic acid (6.1 mL) in N,N-dimethylacetamide (60 mL), followed by stirring the resulting mixture at 100° C. to 105° C. for 7 hours. Ethyl acetate was added to the reaction mixture, and the organic layer was sequentially washed with water and brine, followed by concentration of the organic layer under reduced pressure. The obtained residue was recrystallized from 2-propanol and water to obtain [{(1S,3R,20S)-1,3-dihydroxypregna-5,7,16-triene-20-yl}oxy]-N-(2,2,3,3,3-pentafluoropropyl)acetamide as a gray powder (13.1 g; yield: 46.7%).

Provenance & Evidence