反应详情

温度

0 °C

To a solution of N-(4-((R)-4-((2-(tert-butyldimethylsilyloxy)ethyl)(methyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)-4-(4-((R)-(4′-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzamide (INTERMEDIATE 34, 2.96 g, 2.51 mmol) in dioxane (5.03 ml) and methanol (5.03 ml) was added slowly HCl (4M in dioxane, 15.08 ml, 60.33 mmol). Approximately half way through addition, a slight exotherm was noted, and the reaction was cooled to 0° C. Addition of hydrochloric acid in dioxane (4M) continued, and once complete, the ice bath was removed. The resulting yellow solution was allowed to warm to r.t. and stirred for 3 min before being concentrated under reduced pressure to half volume and diluted with ethyl acetate. The resulting mixture was washed with sodium bicarbonate (saturated, aqueous) and sodium chloride (saturated, aqueous) before being dried over sodium sulfate, filtered, and concentrated. Upon concentration, a thick oily residue precipitated out of solution and this material was redissolved in acetone before being reconcentrated to a beige film. This film was dissolved in 10% methanol in ethyl acetate and purified by column chromatography (ISCO, 330 g SiO2, isocratic 15% methanol in ethyl acetate for 30 min) to afford the title compound (1.90 g, yield: 80%).

1. additionApproximately half way through addition
2. customonce complete, the ice bath was removed
3. temperatureto warm to r.t.
4. concentrationbefore being concentrated under reduced pressure to half volume
5. additiondiluted with ethyl acetate
6. washThe resulting mixture was washed with sodium bicarbonate (saturated, aqueous) and sodium chloride (saturated, aqueous)
7. dry with materialbefore being dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. concentrationUpon concentration
11. customa thick oily residue precipitated out of solution
12. dissolutionthis material was redissolved in acetone
13. dissolutionThis film was dissolved in 10% methanol in ethyl acetate
14. custompurified by column chromatography (ISCO, 330 g SiO2, isocratic 15% methanol in ethyl acetate for 30 min)